2-Acetylaminofluorene: A hepatic carcinogen whose mechanism of activation involves N-hydroxylation to the aryl hydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines.Hydroxyacetylaminofluorene: A N-hydroxylated derivative of 2-ACETYLAMINOFLUORENE that has demonstrated carcinogenic action.Acetoxyacetylaminofluorene: An alkylating agent that forms DNA ADDUCTS at the C-8 position in GUANINE, resulting in single strand breaks. It has demonstrated carcinogenic action.Fluorenes: A family of diphenylenemethane derivatives.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.Liver Neoplasms, Experimental: Experimentally induced tumors of the LIVER.Rats, Inbred F344Diethylnitrosamine: A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.gamma-Glutamyltransferase: An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Precancerous Conditions: Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Benzopyrene Hydroxylase: A drug-metabolizing, cytochrome P-448 (P-450) enzyme which catalyzes the hydroxylation of benzopyrene to 3-hydroxybenzopyrene in the presence of reduced flavoprotein and molecular oxygen. Also acts on certain anthracene derivatives. An aspect of EC A reagent used mainly to induce experimental liver cancer. According to the Fourth Annual Report on Carcinogens (NTP 85-002, p. 89) published in 1985, this compound "may reasonably be anticipated to be a carcinogen." (Merck, 11th ed)DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Nitroanisole O-Demethylase: Oxidative enzyme which transforms p-nitroanisole into p-nitrophenol.Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.Methyldimethylaminoazobenzene: A very potent liver carcinogen.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Hepatectomy: Excision of all or part of the liver. (Dorland, 28th ed)Lipotropic Agents: Endogenous factors or drugs that increase the transport and metabolism of LIPIDS including the synthesis of LIPOPROTEINS by the LIVER and their uptake by extrahepatic tissues.4-Hydroxyaminoquinoline-1-oxide: A potent mutagen and carcinogen. It is a reduction product of 4-NITROQUINOLINE-1-OXIDE. It binds with nucleic acids and inactivates both bacteria and bacteriophage.Aldrin: A highly poisonous substance that was formerly used as an insecticide. The manufacture and use has been discontinued in the U.S. (From Merck Index, 11th ed)Benzopyrenes: A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Liver Regeneration: Repair or renewal of hepatic tissue.Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose.Polydeoxyribonucleotides: A group of 13 or more deoxyribonucleotides in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Aminobiphenyl Compounds: Biphenyl compounds substituted in any position by one or more amino groups. Permitted are any substituents except fused rings.Sulfuric Acids: Inorganic and organic derivatives of sulfuric acid (H2SO4). The salts and esters of sulfuric acid are known as SULFATES and SULFURIC ACID ESTERS respectively.Mutagenicity Tests: Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)DNA Replication: The process by which a DNA molecule is duplicated.Amines: A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)Methylcholanthrene: A carcinogen that is often used in experimental cancer studies.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Nitrophenols

*  2-Acetylaminofluorene - Wikipedia
2-AAF is a substrate for cytochrome P-450 (CYP) enzyme, which is a part of a super family found in almost all organisms. This ... 2-Acetylaminofluorene (AAF, 2-AAF) is a carcinogenic and mutagenic derivative of fluorene. It is used as a biochemical tool in ... The interconversion of amide and amine metabolites of 2-AAF can further occur via the microsomal enzyme deacetylase producing ... The reactive nitrenium, carbonium and arylamidonium ion metabolites of 2-AAF react with the nucleophilic groups in DNA, ...
*  Increased Number of β-Adrenoceptors in Hepatocytes from Rats Treated with 2-Acetylaminofluorene | Cancer Research
Increased Number of β-Adrenoceptors in Hepatocytes from Rats Treated with 2-Acetylaminofluorene. Magne Refsnes, Georg Sager, ... We report that hepatocytes isolated from rats which had been fed 2-AAF (0.025% w/w) for 8-12 weeks had an increased number of β ... For both ligands the number of binding sites was about 4-fold higher in hepatocytes from 2-AAF-treated rats than in those from ... 2 Research fellow of The Norwegian Cancer Society. To whom requests for reprints should be addressed. ...
*  40 CFR Appendix Table 16 to Subpart XXXX of Part 63, Selected Hazardous Air Pollutants | US Law | LII / Legal Information...
This is a list of United States Code sections, Statutes at Large, Public Laws, and Presidential Documents, which provide rulemaking authority for this CFR Part.. This list is taken from the Parallel Table of Authorities and Rules provided by GPO [Government Printing Office].. It is not guaranteed to be accurate or up-to-date, though we do refresh the database weekly. More limitations on accuracy are described at the GPO site. ...
*  ATSDR-PHA-HC-Isla de Vieques Bombing Range, Vieques, Puerto Rico
Florida Tanks (2). Florida. Public water supply tank owned by PRASA. Puerto Rico DOH. June 1999a. ... Table B-2.. Sampling Summary of Groundwater Wells on Isla de Vieques, Puerto Rico. Name. Location. Use. Sampling Agency. ... Well 2-3. Martineau. Remote well used by the public when water supply is interrupted. United States Environmental Protection ... 4-A-DNT was not measured directly, but was considered by Hoffsommer and Glover (1978) to be present at the same levels as 2-A- ...
*  Periodic Table of Elements: Common Compounds of Hydrogen - H (EnvironmentalChemistry.com)
2,4-Diaminoanisole (and its salts). Formula: C7H10N2O. *2,6-Di-tert-butyl-p-cresol. Formula: C15H24O. *2,6-Di-tert-butyl-p- ... Formula: C6H4(CN)2. *m-Toluidine. Formula: CH3C6H4NH2. *m-Xylene. Formula: C6H4(CH3)2. *m-Xylene alpha,alpha'-diaine. Formula: ... Formula: CH3COOCH2CH2CH(CH3)2. *n-Amyl Acetate. Formula: CH3COO[CH2]4CH3. *n-Butyl glycidyl ether. Formula: C7H14O2. *n-Butyl ... Formula: CH2(C6H4NH2)2. *4,4'-Thiobis(6-tert-butyl-m-cresol). Formula: [CH3(OH)C6H2C(CH3)3]2S. *4,5-Dicyanoimidazole. Formula: ...
*  Original list of hazardous air pollutants | Technology Transfer Network Air Toxics Web site | US EPA
n = 1, 2, or 3. R = alkyl or aryl groups. R' = R, H, or groups which, when removed, yield glycol ethers with the structure: R-( ... 2 Includes mono- and di- ethers of ethylene glycol, diethylene glycol, and triethylene glycol R-(OCH2CH2)n -OR' where. ...
*  Patent US5597911 - Mycobacterial nucleic acid hybridization probes and methods of use - Google Patents
2)-3' where formula III represents a polynucleotide containing nucleotides 343-1152 of SEQ ID NO: 3. Primers and probes based ... labelled with acetylaminofluorene, makes it possible, after immunodetection of the hybrids formed, to identify the ... 2. Using dot blot analysis. 10 μl of the amplified samples are denatured by heating at 95 C. for 2 min in 0.2 ml of 0.4M NaOH ... The probes IS-2 (SEQ. ID. NO. 14) and IS-4 (SEQ. ID. NO. 15) are 30 bases in size and are complementary to the fragments ...
*  Chemical Hygiene Plan | Virginia Institute of Marine Science
2. Experience. Summary of prior training and experience :. 3. Personnel participating the work and their prior training and ... 2. Hoods Laboratory hoods with at least 2.5 linear feet of hood space per person should be provided for every 2 workers that ... 2. Eye contact: promptly flush eyes with water for a prolonged period (15 minutes) and seek medical attention. 3. Ingestion: ... 3. Assure that at least 2 persons are present if the material in use is highly toxic or of unknown toxicity. 4. Be prepared for ...
*  Patent US4101673 - Purification of nutritive oils - Google Patents
2. A nutritive oil-in-water emulsion as described in claim 1, wherein said oil is mixed with a solvent at the time it is ... 2 is a photograph of a thin layer silicic acid chromatogram of a sample of the original sunflower oil (A), a sample of the ... sup.2 Tonsil, 60- 90 mesh, Sud Chemie, A. G. .sup.3 Silica Gel, 0.05- 0.2 mm., 70- 325 mesh ASTM, EM Reagent, EM Lab., Inc. . ... 2 is a photograph of a silicic acid thin layer chromatogram of a sunflower oil sample before and after purification on a ...
*  Suse Broyde
Minor-groove binding models for acetylaminofluorene modified DNA.. J Biomol Struct Dyn (1989 Dec) PMID: 2627297. Shapiro R, ... Studies on the conformation and dynamics of the C8-substituted guanine adduct of the carcinogen acetylaminofluorene; model for ... acetylamino)fluorene (dG-N2-AAF).. Chem Res Toxicol (1997 Oct) PMID: 9348435. Grad R, Shapiro R, Hingerty BE, Broyde S ... acetyl)aminofluorene-modified guanine at a mutational hotspot.. Chem Res Toxicol (1998 Nov) PMID: 9815190. Roy D, Hingerty BE, ...
*  Aldehyde dehydrogenase activity in xenografted human brain tumor in nude mice. Preliminary results in human glioma biopsies |...
2.. Hellström E, Tottmar O: Effects of aldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic ... 2.Department of NeuropathologyCentre Hospitalier Universitaire de RennesRennes-CedexFrance ... Lindahl R: Aldehyde dehydrogenase in 2-acetamidofluorene-induced rat hepatomas. Ontogeny and evidence that the new isoenzymes ... Lindahl R: Subeellular distribution and properties of aldehyde dehydrogenase from 2-Acetylaminofluorene-induced rat hepatomas. ...
*  Table of Contents | Cancer Research
Comparison of Oval Cells Induced in Rat Liver by Feeding N-2-Fluorenylacetamide in a Choline-devoid Diet and Bile Duct Cells ... Comparison of Oval Cells Induced in Rat Liver by Feeding N-2-Fluorenylacetamide in a Choline-devoid Diet and Bile Duct Cells ... Noninhibitory Effect of Antioxidants Ethoxyquin, 2(3)-Tert-butyl-4-hydroxyanisole and 3,5-Di-tert-butyl-4-hydroxytoluene on ... Noninhibitory Effect of Antioxidants Ethoxyquin, 2(3)-Tert-butyl-4-hydroxyanisole and 3,5-Di-tert-butyl-4-hydroxytoluene on ...
*  Activity of sulfotransferase 1A1 is dramatically upregulated in patients with hepatocellular carcinoma secondary to chronic...
2. Steck SE, Gaudet MM, Britton JA et al. Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake ... Metabolic processing of 2-acetylaminofluorene by microsomes and six highly purified cytochrome P-450 forms from rabbit liver. ... Elucidation of the effects of the CYP1A2 deficiency polymorphism in the metabolism of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d ... Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase (NAT) 2 polymorphisms and susceptibility to ...
*  N-hydroxy-2-acetamidofluorene reductase - Wikipedia
The systematic name of this enzyme class is 2-acetamidofluorene:NAD(P)+ oxidoreductase. Other names in common use include N- ... In enzymology, a N-hydroxy-2-acetamidofluorene reductase (EC is an enzyme that catalyzes the chemical reaction 2- ... Gutmann HR, Erickson RR (1969). "The conversion of the carcinogen N-hydroxy-2-fluorenylacetamide to o-amidophenols by rat liver ... Kitamura S, Tatsumi K (1985). "Purification of N-hydroxy-2-acetylaminofluorene reductase from rabbit liver cytosol". Biochem. ...
*  Casein - Wikipedia
page 2 Scenic Design And Lighting Techniques: A Basic Guide for Theatre By Chuck B. Gloman, Rob Napoli. Focal Press. 2006. ... 85 (2): 281-94. doi:10.3168/jds.S0022-0302(02)74078-2. PMID 11913691. Holt C (1992). "Structure and stability of bovine casein ... Engel RW, Copeland DH (1 December 1952). "The influence of dietary casein level on tumor induction with 2-acetylaminofluorene ... 2): CD003498. doi:10.1002/14651858.CD003498.pub3. PMC 4164915 . PMID 18425890. Truswell, A.S. (2005), "The A2 milk case: a ...
*  Abstracts of papers not published in full | Proceedings of the Indiana Academy of Science
2-Acetylaminofluorene in the Rat. Sandra Schiller-Smith, David Nowack, William L. Elliott, Peter F.. Heinstein and D. James ... Cyclic Nucleotide Changes During 2-Acetylaminofluorene Induced. Hepatocarcinogensis in the Rat. Robert J. Stark. Changes in ...
*  A sub-population of rat liver membrane-bound ribosomes that are detached in vitro by carcinogens and centrifugation |...
Incubation of postmitochondrial supernatant with 0.2 mM-diethylnitrosamine or N-2-acetylaminofluorene removed approx. 16% of ...
*  Table of Contents | Cancer Research
Effect of N-2-Acetylaminofluorene Modification on the Structure and Template Activity of DNA and Reconstituted Chromatin ... Biological and Biochemical Properties of 1-(2-Chloroethyl)-3-(β-d-glucopyranosyl)-1-nitrosourea (NSC D 254157), a Nitrosourea ... of a Marginally Lipotrope-deficient Diet on the Hepatic Levels of S-Adenosylmethionine and on the Urinary Metabolites of 2- ... Acetylaminofluorene in Rats. Lionel A. Poirier, Preston H. Grantham and Adrianne E. Rogers ...
*  Plus it
Five of these six compounds are hydroxylated compounds, and the other is N-acetoxy-2-acetylaminofluorene. From these ...
*  Patent US7790183 - Combination of antimicrobial agents and bacterial interference to coat ... - Google Patents
2. *. Alekshun et al, Biochemical Pharmacology, 2006, 71:893-900.. 3. *. Bergogne-Berezin et al, J. Hospital Infection, 1995, ... 2 Mar 1962. 26 Jul 1966. Ile De Rech S Scient Et Ind So. Procedure for developing antimicrobial activity in non-pathogenic ... 1994, 4/Supplement 2:S21-S27 abstract only.. 29. Nayir et al, "The Effects of Vaccination with Inactivated Uropathogenic ... 2. The method of claim 1. , wherein said antimicrobial agent is selected from the group consisting of an antibiotic, an ...
*  Susceptibility of Human Lymphocytes to 2-Nitrofluorene-Induced Gene Mutation is Strongly Dependent on Metabolic Genotypes |...
2ARUP Laboratories, Salt Lake City, Utah, USA. *Corresponding Author:. Dr. Saimei Hou. Department of Biosciences and Nutrition ... The ability of 2-NF and N-hydroxylated AAF to revert the lacZ mutation in Escherichia coli by -2 frameshift was strongly ... Sai-Mei Hou1*, Tatiana Tvrdik2 and Lennart Möller1. 1Department of Biosciences and Nutrition, Karolinska Institutet, 14157 ... The cells were exposed to 2-NF (400 μg/mL, Sigma-Aldrich) for 24 hours at 37°C with 5% CO2. After washing with PBS, the cells ...
*  CiNii 論文 - Role of Point Mutation of the K-ras Gene in Tumorigenesis of B6C3F 1 Mouse Lung...
ras mutations in 2-acetylaminofluorene-induced lung and liver tumors from C3H/HeJ and (C3H × A/J)F_1 mice WANG Yu. ... 2. Designed diagnostic restriction fragment length polymorphisms for the detection of point mutations in ras oncogenes KUMAR R ... Mutational analysis of a dominant oncogene (c-Ki-ras-2) and a tumor suppressor gene (p53)in hamster lung tumorigenesis OREFFO V ... 2. POSSIBLE MECHANISM ON ENHANCED CARCINOGENESIS OF GENOTOXIC CARCINOGENS AND UNSOLVED MECHANISMS ON LESSER CARCINOGENIC ...
*  Ames test - Wikipedia
Examples include tris(2,3-dibromopropyl)phosphate, which was used as a flame retardant in plastic and textiles such as ... 455 (1-2): 29-60. doi:10.1016/S0027-5107(00)00064-6. PMID 11113466. Charnley G (2002). "Ames Test". Encyclopedia of Public ... ISBN 0-470-49919-2. Tubiana, M. (1992). "The carcinogenic effect of exposure to low doses of carcinogens". British journal of ... Prival, M.; McCoy, E.; Gutter, B; Rosendranz, H. (1977). "Tris(2,3-dibromopropyl) phosphate: Mutagenicity of a widely used ...
*  SULT1C2 - Wikipedia
129 (1-2): 141-70. doi:10.1016/S0009-2797(00)00202-7. PMID 11154739. Glatt H, Boeing H, Engelke CE, Ma L, Kuhlow A, Pabel U, ... 482 (1-2): 27-40. doi:10.1016/S0027-5107(01)00207-X. PMID 11535246. Kiehlbauch CC, Lam YF, Ringer DP (August 1995). " ... 65 (2): 157-65. doi:10.1006/geno.2000.6150. PMID 10783263. "Entrez Gene: SULT1C1 sulfotransferase family, cytosolic, 1C, member ... doi:10.1016/S1357-2725(99)00038-2. PMID 10481272. Li X, Clemens DL, Anderson RJ (December 2000). "Sulfation of iodothyronines ...

HydroxyacetylaminofluoreneAcetoxyacetylaminofluoreneBenzo(a)fluoreneCarcinogen: A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes.Dena A. Smith: Dena A. Smith (October 19, 1899 – February 20, 1968) was the state treasurer of Wisconsin from 1957 to 1959 and from 1961 until her death in office in 1968.Liver sinusoid: A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.SIU SOM Histology GINucleoside phosphoramiditeBiotransformation: Biotransformation is the chemical modification (or modifications) made by an organism on a chemical compound. If this modification ends in mineral compounds like CO2, NH4+, or H2O, the biotransformation is called mineralisation.Liver function tests: LFT}}Epithelial dysplasia: Epithelial dysplasia, a term becoming increasingly referred to as intraepithelial neoplasia, is the sum of various disturbances of epithelial proliferation and differentiation as seen microscopically. Individual cellular features of dysplasia are called epithelial atypia.Mutagen: In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer, mutagens are therefore also likely to be carcinogens.BenzopyreneDNA condensation: DNA condensation refers to the process of compacting DNA molecules in vitro or in vivo. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems.Benzo(e)pyreneMicrosome: In cell biology, microsomes are vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.Flow focusingAldrin (disambiguation): Aldrin is a pesticide.Deoxyguanosine diphosphateBase excision repair: frame|right|Basic steps of base excision repair|Basic steps of base excision repairWet sulfuric acid process: The wet sulfuric acid process (WSA process) is one of the key gas desulfurization processes on the market today. Since the Danish catalyst company Haldor Topsoe introduced and patented this technology in the late 1980s, it has been recognised as an efficient process for recovering sulfur from various process gasses in the form of commercial quality sulfuric acid (H2SO4), with simultaneous production of high pressure steam.Hydroxylation: Hydroxylation is a chemical process that introduces a hydroxyl group (-OH) into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases.DNA re-replication: DNA re-replication (or simply rereplication) is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers.Organic base: An organic base is an organic compound which acts as a base. Organic bases are usually, but not always, proton acceptors.G2-M DNA damage checkpoint: The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms ranging from yeast to mammals. This checkpoint ensures that cells don't initiate mitosis before they have a chance to repair damaged DNA after replication.

(1/450) Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice.

Mice that are genetically engineered to mimic the human hereditary cancer-prone DNA repair-defective disease xeroderma pigmentosum (XP) are highly predisposed to UV radiation-induced skin cancer. It is not clear, however, whether XP mice or humans are predisposed to cancers in other tissues associated with exposure to environmental carcinogens. To test the importance of nucleotide excision repair in protection against chemical carcinogenesis in internal organs, we treated XPC mutant (XPC-/-) mice with 2-acetylaminofluorene and NOH-2-acetylaminofluorene. We observed a significantly higher incidence of chemically induced liver and lung tumors in XPC-/- mice compared with normal and heterozygous littermates In addition, the progression of liver tumors in XPC-/- Trp53+/- mice is accelerated compared with XPC-/- Trp53+/+ animals. Finally, we demonstrate a higher incidence of spontaneous testicular tumors in XPC-/- TrpS3-/- double mutant mice compared with XPC+/+ Trp53-/- mice.  (+info)

(2/450) Pseudoenzymatic reduction of N-hydroxy-2-acetylaminofluorene to 2-acetylaminofluorene mediated by cytochrome P450.

N-hydroxy-2-acetylaminofluorene (N-OH-AAF) was reduced to 2-acetylaminofluorene by rat liver microsomes in the presence of both NAD(P)H and FAD under anaerobic conditions. The microsomal reduction proceeds as if it were an enzymatic reaction. However, when the microsomes were boiled, the activity was not abolished, but was enhanced. The activity was also observed with cytochrome P450 2B1 alone, without NADPH-cytochrome P450 reductase, in the presence of these cofactors. Hematin also exhibited a significant reducing activity in the presence of both a reduced pyridine nucleotide and FAD. The activities of microsomes, cytochrome P450 2B1 and hematin were also observed upon the addition of photochemically reduced FAD instead of both NAD(P)H and FAD. The microsomal reduction of N-OH-AAF appears to be a non-enzymatic reaction by the reduced flavin, catalyzed by the heme group of cytochrome P450.  (+info)

(3/450) Effect of detergents on the N-and ring-hydroxylation of 2-acetamidofluorene by hamster liver microsomal preparations.

Effects of detergents such as cholate, deoxycholate and Triton X-100 were studied on N-and ring-hydroxylation of 2-acetamidofluorene by reconstituted and unresolved microsomal systems from livers of hamsters pretreated with 3-methylcholanthrene. Triton X-100 (2.5 mg/nmol of cytochrome P-448) inhibited N-and ring-hydroxylation by wholemicrosomal preparations by 40 and 90% respectively Deoxycholate at the same concentration inhibited both hydroxylations completely, whereas cholate inhibited N-and ring-hydroxylation by 40 and 50% respectively. In reconstitution studies, the presence of Triton X-100(0.5-1.0mg/nmol of cytochrome P-448) along with unsolubilized cytochrome P-448 fraction and solubilized reductase fraction increased N-hydroxylation to an appreciable extent compared with ring-hydroxylation. Both cholate and deoxycholate at 0.5-1.0 mg concentrations had a greater stimulatory effect on ring-than on N-hydroxylation activity in such a reconstituted system.  (+info)

(4/450) Bone marrow as a potential source of hepatic oval cells.

Bone marrow stem cells develop into hematopoietic and mesenchymal lineages but have not been known to participate in production of hepatocytes, biliary cells, or oval cells during liver regeneration. Cross-sex or cross-strain bone marrow and whole liver transplantation were used to trace the origin of the repopulating liver cells. Transplanted rats were treated with 2-acetylaminofluorene, to block hepatocyte proliferation, and then hepatic injury, to induce oval cell proliferation. Markers for Y chromosome, dipeptidyl peptidase IV enzyme, and L21-6 antigen were used to identify liver cells of bone marrow origin. From these cells, a proportion of the regenerated hepatic cells were shown to be donor-derived. Thus, a stem cell associated with the bone marrow has epithelial cell lineage capability.  (+info)

(5/450) Resistance to the promotion of glutathione S-transferase 7-7-positive liver lesions in Copenhagen rats.

Previously, we have shown that Copenhagen (Cop) rats are highly resistant to the induction of putative preneoplastic, glutathione S-transferase 7-7 (GST 7-7)-positive liver lesions following treatment with a modified resistant hepatocyte protocol. The objective of the current study was to establish the time course for the development of resistance and examine potential resistance mechanisms in Cop rats using F344 rats as susceptible controls. Male Cop and F344 rats (n = 25), 7-8 weeks of age, were initiated with diethylnitrosamine (200 mg/kg) and promoted 3 weeks later with four doses of 2-acetylaminofluorene (20 mg/kg) and a 2/3 partial hepatectomy (PH). Groups of rats from each strain were killed on days 2, 4, 7, 14 and 21 post-PH, 2 h after receiving bromodeoxyuridine. Cop livers contained similar numbers of GST 7-7-positive lesions to F344 livers on days 2 and 4 post-PH. The percent volume of liver occupied by these lesions did not differ between the strains on days 2, 4 and 7 post-PH. On day 14, however, approximately 29% of the liver volume in F344 rats was occupied by lesions, whereas in Cop rats this was significantly less (approximately 9%, P < 0.001). On day 21, lesions occupied approximately 58% of F344 rat livers and only approximately 6% of Cop livers. Despite these differences, the labeling index of hepatocytes was not significantly different between the strains at any time point, either within lesions or within surrounding normal liver. Furthermore, the apoptotic indices were not different between the strains at any time. However, differences were found in the extent of lesion remodeling (redifferentiation) and in the pattern of oval cell response following PH in Cop livers. By day 14 post-PH, approximately 76% of Cop liver lesions showed evidence of remodeling, compared with only approximately 14% of F344 lesions. The oval cell response to PH was equivalent in the two strains up to day 4 post-PH but by day 7, in F344 livers there was extensive migration of these cells into the liver parenchyma, whereas in Cop livers, the response remained localized to the portal regions. These results suggest that Cop resistance occurs at the promotion stage and not the initiation stage of carcinogenesis. Resistance appears not to be due to a lower proliferation rate nor to a higher apoptotic rate within Cop lesions. Precocious remodeling and/or a diminished oval cell response, however, may contribute to the resistance of Cop rats to the growth of GST 7-7-positive hepatic lesions.  (+info)

(6/450) Analysis of loss of heterozygosity in neoplastic nodules induced by diethylnitrosamine in the resistant BFF1 rat strain.

Loss of heterozygosity (LOH) at specific chromosomal regions is a frequent event in poorly differentiated human hepatocellular carcinomas (HCCs), but rare in mouse HCCs. This behavior could depend on interspecies differences in mechanisms of hepatocarcinogenesis or in developmental stage of lesions. To verify if LOH is involved in rat hepatocarcinogenesis, we studied LOH frequency in slowly growing neoplastic nodules induced by Solt-Farber model in diethylnitrosamine-initiated BFF1 rats. We analyzed, with microsatellites, markers at 67 rat loci dispersed over all chromosomes, corresponding to regions homologous to those lost in human HCCs or containing hepatocellular susceptibility (Hcs) or resistance (Hcr) loci in rat and mouse. In agreement with previous findings with mouse HCCs, but at variance with human HCCs, no detectable LOH was found at any locus in rats, suggesting rare LOH involvement in neoplastic nodules, with low tendency to progress to full malignancy, of BFF1 rats.  (+info)

(7/450) Development of resistance during the early stages of experimental liver carcinogenesis.

The present study was designed to determine whether the resistant phenotype is acquired at the initiated cell stage itself or requires further exposure to a promoting regimen to express resistance. Male Fischer 344 rats were initiated with diethylnitrosamine (DENA) (200 mg/kg i.p.) and were subjected to either no further treatment or to the resistant hepatocyte (RH) model of liver tumor promotion. Six weeks later, the resistance of the focal lesions generated in these two groups to the mitoinhibitory effects of 2-acetylaminofluorene (2-AAF) was determined by subjecting the rats to two-thirds partial hepatectomy (PH) in the presence of a mitoinhibitory dose of 2-AAF (5 mg/kg i.p.) given at the time of PH. Labeling index was determined by administering multiple injections of [(3)H]thymidine. All rats were killed 48 h post-PH. While only a small percentage (23%) of the glutathione S-transferase-positive foci generated by DENA in the absence of an exogenous liver tumor promoting regimen were resistant to the mitoinhibitory effects of 2-AAF, a majority (85%) of the foci became resistant to 2-AAF following exposure to the RH model of liver tumor promotion. Further, initiated rats exposed to either 2-AAF or to CCl(4) alone, the two components of the RH model, resulted in 71% of the foci being resistant to the mitoinhibitory effects of 2-AAF. Similar patterns of results were obtained when the resistance of the foci to the mitoinhibitory effects of orotic acid, a liver tumor promoter and an inhibitor of DNA synthesis in normal hepatocytes, was monitored. These results suggest that the majority of initiated hepatocytes are not of resistant phenotype, however, they have acquired a unique ability to express resistance upon exposure to certain agents such as 2-AAF and CCl(4) or to a promoting regimen such as the RH model of liver tumor promotion.  (+info)

(8/450) Modulation of the gene network connected to interferon-gamma in liver regeneration from oval cells.

Suppression subtractive hybridization was used to clone genes associated with proliferation of oval cells in rat liver regenerating after a 70% partial hepatectomy combined with the feeding of 2-acetylaminofluorene. A subset of the identified genes comprised interferon-gamma receptor alpha subunit (IFN-gammaRalpha), gp91phox, interleukin-1beta (IL-1beta), lymphocyte function-associated molecule-1alpha (LFA-1), eukaryotic initiation factor-2-associated 67-kd protein (eIF-2-associated 67-kd protein), and alpha-fetoprotein, which constitute part of the cellular program modulated by IFN-gamma. Therefore, expression analysis performed by Northern blotting and immunohistochemistry were extended to include IFN-gamma, the IFN-gamma receptor beta subunit (IFN-gammaRbeta), three secondary response genes induced by interaction of IFN-gamma with IFN-gamma receptor complexes, ie, IL-1beta-converting enzyme (ICE), intercellular adhesion molecule-1 (ICAM-1), and urokinase-type plasminogen activator receptor (uPAR), and a cytokine inducing IFN-gamma expression, ie, interleukin-18 (IL-18). The Northern blot analysis showed that all examined genes were modulated when progenitor-like oval cells were activated and recruited for liver regeneration. Immunohistochemistry localized the subunits of the IFN-gamma receptor complex, IFN-gammaRalpha and IFN-gammaRbeta, the secondary response genes uPAR and ICAM-1, the IFN-gamma-inducing factor IL-18, and ICE to the ductular structures of oval cells. In contrast, during liver regeneration after a 70% partial hepatectomy, only modulation of IL-1beta and ICE was observed. Our results, therefore, indicate that IFN-gamma-mediated events may be particularly important when cells in the bile ductules must respond to liver damage by production of ductular oval cells.  (+info)

  • rats
  • We report that hepatocytes isolated from rats which had been fed 2-AAF (0.025% w/w) for 8-12 weeks had an increased number of β-adrenoceptors, as determined by [ 3 H]dihydroalprenolol binding to whole cells and [ 125 I]iodocyanopindolol binding to washed particles. (aacrjournals.org)
  • For both ligands the number of binding sites was about 4-fold higher in hepatocytes from 2-AAF-treated rats than in those from controls. (aacrjournals.org)
  • enzyme
  • 2-AAF is a substrate for cytochrome P-450 (CYP) enzyme, which is a part of a super family found in almost all organisms. (wikipedia.org)
  • In addition, the cytosolic N,O-aryl hydroxamic acid acyltransferase enzyme catalyzes the transfer of the acetyl group from the N atom of the N-OH-2-AAF to the O atom of the N-OH group to produce N-acetoxy-2-aminofluorene (N-OH-2-AF). (wikipedia.org)
  • In enzymology, a N-hydroxy-2-acetamidofluorene reductase (EC is an enzyme that catalyzes the chemical reaction 2-acetamidofluorene + NAD(P)+ + H2O ⇌ {\displaystyle \rightleftharpoons } N-hydroxy-2-acetamidofluorene + NAD(P)H + H+ The 4 substrates of this enzyme are 2-acetamidofluorene, NAD+, NADP+, and H2O, whereas its 4 products are N-hydroxy-2-acetamidofluorene, NADH, NADPH, and H+. (wikipedia.org)
  • The systematic name of this enzyme class is 2-acetamidofluorene:NAD(P)+ oxidoreductase. (wikipedia.org)
  • nucleotide
  • 2. The DNA of claim 1, consisting of the nucleotide sequence of SEQ ID NO:4. (google.com)
  • Structural basis for the recognition of diastereomeric 5',8-cyclo-2'-deoxypurine lesions by the human nucleotide excision repair system. (nyu.edu)
  • include
  • Other names in common use include N-hydroxy-2-acetylaminofluorene reductase, and NAD(P)H:N-hydroxy-2-acetamidofluorene N-oxidoreductase. (wikipedia.org)
  • Examples include tris(2,3-dibromopropyl)phosphate, which was used as a flame retardant in plastic and textiles such as children's sleepwear, and furylfuramide which was used as an antibacterial additive in food in Japan in 1960s and 1970s. (wikipedia.org)
  • found
  • 1960), who found that N-hydroxy-2-acetylaminofluorene was formed in the intact rat upon administration of 2-acetylaminofluorene. (wikipedia.org)
  • Glycine, formate, and the 2-carbon of serine were all found to be very quickly incorporated into hadacidin during its synthesis by Penicillium aurantioviolaceum. (wikipedia.org)
  • The experiment showed that C-1 of glycine was found almost exclusively in the glycyl portion of hadacidin while formate, the 3-carbon of serine, and the 2-carbon of glycine were incorporated into both the glycyl and formyl portions of the hydroxamate. (wikipedia.org)