• Significant exposure to Aflatoxin B 1 (AFB 1 ), a potent hepatotoxic and hepatocarcinogenic mycotoxin, plays a major role in liver carcinogenesis through oxidative tissue damage and p53 mutation. (hindawi.com)
  • AFB 1 induces lipid peroxidation in rat liver, and this may be an underlying mechanism of carcinogenesis [ 7 ]. (hindawi.com)
  • DNA adducts have been detected at low levels in human endometrium, and there is much interest in determining whether DNA damage plays a role in tamoxifen-induced endometrial carcinogenesis. (mssm.edu)
  • Indole-3-carbinol as a chemopreventive agent in 2-amino-1-methyl-6-phenylimidazo [4,5-b pyridine (PhIP) carcinogenesis: inhibition of PhIP-DNA adduct formation, acceleration of PhIP metabolism, and induction of cytochrome P450 in female F344 rats. (vitaminwiki.net)
  • Oxidative damage to DNA, and/or the direct adduction of reactive molecules to DNA, such as can occur with formaldehyde, is the most important intermediate outcome of chemical carcinogenesis. (nationalacademies.org)
  • Natural chlorophyll inhibits dibenzo[a,l]pyrene-induced liver and stomach carcinogenesis in rainbow trout[J]. Cancer Research, 2006, 66. (boysandgirlsclubofcypress.com)
  • 2002). Measuring hemoglobin adducts, an extremely sensitive effect biomarker, which does not undergo repair as DNA-adducts, may overcome this problem. (cdc.gov)
  • An increased incidence of tumours was reported in multiple tissues, such as the mesothelial tissues (tunica vaginalis of the testis, epididymis, abdominal wall or surface of abdominal organs), skin (subcutaneous tissues), mammary gland, liver and lungs, in rats exposed via the diet. (gc.ca)
  • We previously showed that mammosphere-derived epithelial cells from species with low mammary cancer incidence, such as horses, respond to carcinogen 7, 12-Dimethylbenz(a)anthracene-induced DNA damage by undergoing apoptosis, a postulated anti-cancer mechanism. (bvsalud.org)
  • Effects of indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC) on 7,12-dimethylbenz[aanthracene (DMBA)-induced DNA adducts in rat mammary glands and liver (Meeting abstract). (vitaminwiki.net)
  • CYP1A1 and CYP1B1 gene expression and DNA adduct formation in normal human mammary epithelial cells exposed to benzo[a]pyrene in the absence or presence of chlorophyllin. (boysandgirlsclubofcypress.com)
  • Once bioactivated, MeIQx metabolites can lead to DNA adduct formation responsible for further genome instability. (peerj.com)
  • We investigated the cytotoxicity, DNA-damaging potential, and mitochondrial damage of HAAs and their genotoxic HONH-HAA metabolites in galactose-dependent SH-SY5Y cells, a human neuroblastoma cell line relevant for PD-related neurotoxicity. (bvsalud.org)
  • Platforms based on thin enzyme/DNA films were used in two-tier screening of chemicals for reactive metabolites capable of producing toxicity. (uconn.edu)
  • When bioactivation of substrates in the films gives reactive metabolites, they are trapped by covalent attachment to DNA bases. (uconn.edu)
  • Toxic hits" uncovered by the array were studied in structural detail by using enzyme/DNA films on silica nanospheres as "nanoreactors" to provide nucleobase adducts from reactive metabolites. (uconn.edu)
  • Reactive quinone and epoxide metabolites of similar compounds, such as benzo[a]pyrene, have been shown to enact their carcinogenecity through DNA adduct formation. (nih.gov)
  • Graduate research activities involving mechanistic studies on xenobiotic toxicity invariably expose students to the field of drug metabolism, particularly in cases where xenobiotics are enzymatically bioactivated to electrophilic reactive metabolites that can covalently adduct to proteins and DNA and cause toxicity. (aspetjournals.org)
  • Metabolism and chemical binding to DNA (adduct formation) are critical in cancer induction by NNK and NNN. (wikipedia.org)
  • This ultimately results in membrane damage, fragmentation, or random cross-linking of molecules like DNA, enzymes, and structural proteins and even lead to cell death induced by DNA fragmentation, lipid peroxidation and finally to cancer formation [ 15 ]. (hindawi.com)
  • DNA adduct formation pathway through the prediction of potential genotoxic compounds) and detoxification of MeIQx in order to predict the behaviour of this environmental contaminant in the human liver. (peerj.com)
  • This experiment was conducted to assess formation of N-nitroso compounds in the stomach, and to detect DNA adduct generation in target organs by immunohistochemical staining. (europa.eu)
  • Click links below to explore KE 373, Formation, Pro-mutagenic DNA Adducts in tools offered by third parties. (aopwiki.org)
  • HONH-PhIP DNA adduct formation occurred at 300-fold higher levels than adducts formed with HONH-MeIQx and HONH-AαC, assuming similar cellular uptake rates. (bvsalud.org)
  • Relative enzyme turnover rates for these compounds using ECL arrays and LC-UV-MS correlated well with TD 50 values for liver tumor formation in rats. (uconn.edu)
  • There is direct evidence of tumor formation in mice and rats but no direct evidence of carcinogenecity of NA in humans at this time. (nih.gov)
  • TAM ( a ) proceeds four steps leading to genotoxicity which are 1) α-hydroxylation by cytochrome p450, 2) sulfonation by sulfotransferase (SULT), and 3) formation of carbocation to react with DNA, particularly with 2′-deoxyguanosine (dG) [ 11 ]. (biomedcentral.com)
  • Anti-angiogenic therapy is an old method to fight cancer that aims to abolish the nutrient and oxygen supply to the tumor cells through the decrease of the vascular network and the avoidance of new blood vessels formation. (mdpi.com)
  • Kinetics of DNA adduct formation and removal in mouse hepatocytes following in vivo exposure to 5,9-dimethyldibenzo[c,g]carbazole. (shengsci.com)
  • To gain insight into the mechanisms underlying the mutagenicity of DMDBC in vivo, DNA damage formation and removal were monitored in m. (shengsci.com)
  • In vivo , Pts treatment effectively protected against APAP-induced severe liver injury by decreasing the lethality rate, the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, liver histological injury, liver malondialdehyde (MDA) formation and myeloperoxidase (MPO) levels and by increasing liver glutathione (GSH) and superoxide dismutase (SOD) levels. (karger.com)
  • Extracts of raw oil shale from Scotland (UK) and the Green River Formation (USA) were tested by skin application in mice, and no skin tumour was observed. (europa.eu)
  • NNN is an effective esophageal carcinogen in the rat, and induces respiratory tract tumors in mice, hamsters, and mink. (wikipedia.org)
  • Tumours in the circulatory system, large intestine and liver were reported in mice exposed via the dietary route as well. (gc.ca)
  • The animal data consist of oral, inhalation and subcutaneous studies in three strains of rats and two strains of mice. (cdc.gov)
  • Chronic inflammation in mice model that are initiated by the DSS causes colitis, deoxyribonucleic acid (DNA) damage and encourages the emergence of adenoma [ 11 , 12 ]. (biomedcentral.com)
  • Prior work has demonstrated that food restriction of mice markedly suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion of skin papillomas and adrenalectomy prior to initiating food restriction completely reverses the tumor inhibitory effect of underfeeding. (shengsci.com)
  • In the present experiment the effect of food restriction, with or without prior adrenalectomy, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tumor development in A/J mice was explored. (shengsci.com)
  • Food restriction (27%), beginning 3 weeks after a single oral dose of 0.5 mg DMBA and continued for the duration of the experiment (14 weeks), significantly inhibited lung adenoma development, whereas adrenalectomy 2 weeks before initiating food restriction abolished the tumor inhibitory effect of underfeeding and also enhanced tumor development in the ad libitum fed mice. (shengsci.com)
  • These studies suggest that adrenal gland secretory products may play a general role in the tumor preventive effect of food restriction in laboratory mice. (shengsci.com)
  • NNK and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are potent systemic lung carcinogens in rats. (wikipedia.org)
  • 97 %) was administered in the diet to male Fischer rats at approximately 220 mg/kg bw for a period of 23 weeks in combination with (i) a preceding 4-week initiation phase characterised by a treatment with 6 known carcinogens and/or (ii) sodium nitrite concurrently given in the drinking water for 23 weeks. (europa.eu)
  • Rats were treated with 6 carcinogens targeting different organs. (europa.eu)
  • PhIP-DNA adduct levels occurred at concentrations as low as 1 nM and were threefold or higher and more persistent in mitochondrial DNA than nuclear DNA. (bvsalud.org)
  • N-Acetyltransferases (NATs), sulfotransferases, and kinases catalyzed PhIP-DNA binding and converted HONH-PhIP to highly reactive ester intermediates. (bvsalud.org)
  • This study investigates the mutagenicity of tamoxifen DNA adducts formed by α-acetoxytamoxifen, a reactive ester producing the major DNA adduct formed in livers of tamoxifen-treated rats. (mssm.edu)
  • Tumors of the nasal cavity, liver, and pancreas are also observed in NNK- or NNAL-treated rats. (wikipedia.org)
  • Propylene oxide caused tumors at or near the site of administration in rodents, causing nasal tumors after inhalation exposure (NTP, 1985). (cdc.gov)
  • 1995. Relating aromatic hydrocarbon-induced DNA adducts and c-H-ras mutations in mouse skin papillomas. (cdc.gov)
  • G to T transversion mutations in codon 249 of the p53 tumour-suppressor gene have been found in human liver tumour from geographic areas with high risk of aflatoxin exposure and in AFB 1 -induced liver toxicity [ 8 ]. (hindawi.com)
  • Relative mutation frequencies increased with the adduct level, with 1.3-3.6-fold higher numbers of mutations in the XP cells compared to the GM00637 cells, indicating that NER plays a significant role in the removal of these particular tamoxifen DNA adducts. (mssm.edu)
  • In both cell lines, as the adduct level increased, the proportion of GC → AT transitions decreased and GC → TA transversions, mutations known to arise from the major tamoxifen adducts, increased. (mssm.edu)
  • To define NA-adapted, sensitive, and predictive genotoxicity screening tools, both DNA base mutations and DNA repair-dependent DNA strand breaks serve as endpoints. (fraunhofer.de)
  • Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for around 70% of all liver cancers [ 1 ]. (hindawi.com)
  • Histological observation confirmed the induction of tumour in Group II animals and complete regression of tumour in Group III animals. (hindawi.com)
  • No clear treatment-related induction of liver tumours was found. (europa.eu)
  • Supplementation with SCC before meals substantially decreased a urinary biomarker of aflatoxin-induced DNA damage in a Chinese population at high risk of liver cancer due to unavoidable, dietary aflatoxin exposure from moldy grains and legumes . (oregonstate.edu)
  • Major target organs were liver, forestomach and epidermal structures, of which the liver is considered the most relevant for human risk assessment in terms of pathogenesis and sensitivity. (europa.eu)
  • However, oxidative stress has emerged as a key player in the development and the progression of liver cirrhosis [ 4 ] which is known to be a precursor of HCC. (hindawi.com)
  • Bansal AK, Bansal M, Soni G, Bhatnagar D . Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver. (jcimjournal.com)
  • Functional assays confirmed impaired DNA binding of mutated RBPJ, placing it among other notch-pathway Selleckchem Galardin proteins altered in human genetic syndromes. (phosphorylase-signal.com)
  • Metabolic pathway of TAM leading to DNA modification was shown in Fig. 1 . (biomedcentral.com)
  • In CAC, intestinal inflammation play critical role that induce DNA damage and cellular proliferation pathway. (biomedcentral.com)
  • Free radicals can cause damage in structural and metabolic components like lipids, proteins, enzymes, carbohydrates and DNA in cells and tissues. (hindawi.com)
  • Out of selleck Dabrafenib 76 differentially expressed proteins, 6 proteins ATPD, FIBB, ATPB, HBB, CYB5A, and QCR1 were quantified across the specimens and delineated into liver fibrosis and carcinoma unique pro teins. (kspinhibitors.com)
  • This CAC is associated with the cell cycle and its regulation is affected by the tumor suppressor proteins. (biomedcentral.com)
  • 2-Nitrotoluene was genotoxic in a range of in vitro and in vivo assays, was notably clastogenic in human peripheral lymphocytes and formed DNA adducts in exposed rodents. (gc.ca)
  • RTOG 0417 was a development II study of 49 patients treated with bevacizumab in combination with concurrent radiotherapy and cisplatin in stage IIBВ-IIIB infirmity or IBВ-IIA disease with biopsy-proven pelvic nodal metastasis and/or tumor size of at least 5 cm [53]. (daubnet.com)
  • A control group (n=30) with the same tumour and nodal staging was treated with a usual cisplatin solution (150 mg m(-2) dissolved in 500 ml saline). (omicsdi.org)
  • AFB 1 -administered HCC-bearing rats (Group II) showed increased levels of lipid peroxides (LPOs), thiobarbituric acid substances (TBARs), and protein carbonyls (PCOs) and decreased levels of enzymic and nonenzymic antioxidants when compared to control animals (Group I). Administration of TD orally (300 mg/kg body weight/day) for 45 days to HCC-bearing animals (Group III) significantly reduced the tissue damage accompanied by restoration of the levels of antioxidants. (hindawi.com)
  • This study demonstrated the carcinogenic potential of the test material in a variety of organs when administered by gavage to rats. (europa.eu)
  • As an alternative tool, they investigate the sensitivity and predictivity of the in-vitro alkaline comet assay with different liver cell models (HepG2 cells, primary rat and human hepatocytes). (fraunhofer.de)
  • Using a computational approach, we developed a numerical model for MeIQx metabolism in the liver that predicts the MeIQx biotransformation into detoxification or bioactivation pathways according to the concentration of MeIQx. (peerj.com)
  • Synergistic Metabolic Toxicity Screening Using Microsome/DNA Electroch" by Sadagopan Krishnan, Eli G. Hvastkovs et al. (uconn.edu)
  • and Rusling, James F., "Synergistic Metabolic Toxicity Screening Using Microsome/DNA Electrochemiluminescent Arrays and Nanoreactors" (2008). (uconn.edu)
  • However, tamoxifen causes hepatic carcinomas in rats through a genotoxic mechanism and increases the risk of endometrial tumors in women. (mssm.edu)
  • Mitochondrial respiratory chain complex dysfunction and DNA damage are major mechanisms in PD pathogenesis. (bvsalud.org)
  • The rate of increase in ECL with enzyme reaction time reflects relative DNA damage rates. (uconn.edu)
  • The utility of this synergistic approach was demonstrated by estimating relative DNA damage rates of three mutagenic N -nitroso compounds and styrene. (uconn.edu)
  • V. Effect on peroxidative damage of rat liver lysosomes. (boysandgirlsclubofcypress.com)
  • MeIQx is metabolized by cytochrome P450 1A2 in the human liver into detoxificated and bioactivated products. (peerj.com)
  • Levels of xenobiotic metabolizing enzymes such as cytochrome (Cyt) P450 and Cyt b5, activities of reduced glutathione (GSH), glutathione-S-transferase (GST), aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) and alkaline phosphatase (ALP), and total protein and cholesterol content in the liver tissues were measured to determine the hepatotoxicity caused by DENA. (jcimjournal.com)
  • Twenty-five of these cell cultures stemmed from normal and 21 from tumor tissues. (shengsci.com)
  • 1989), male and female Sprague Dawley rats were exposed via inhalation to 0, 36, 181 or 543 mg/m3 Morpholine (99.2 %) for 6 hours a day, 5 days per week for 52 (interim sacrifice) or 104 weeks (terminal sacrifice). (europa.eu)
  • Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. (aacrjournals.org)
  • Ultrafine Particulate Matter Combined With Ozone Exacerbates Lung Injury in Mature Adult Rats With Cardiovascular Disease. (ucdavis.edu)
  • Adducted plasmids were transfected into nucleotide excision repair proficient (GM00637) or deficient (GM04429, XPA) human fibroblasts. (mssm.edu)
  • Differences in the corresponding DNA repair processes are investigated by using repair-proficient as well as repair-deficient human and mouse cell models. (fraunhofer.de)
  • The N -hydroxyarylamines undergo ac- id-catalysed reactions with DNA to form a variety of DNA adducts. (who.int)
  • However, the pre-supplementation of HEEN showed a remarkable amelioration of these abnormalities, and the levels of the antioxidant enzymes in the liver were significantly restored, which exhibited the dose-dependent protective effect against DENA-induced hepatotoxicity. (jcimjournal.com)
  • DNA binding assays with cytosolic, mitochondrial, and nuclear fractions of SH-SY5Y fortified with cofactors revealed that cytosolic AcCoA-dependent enzymes, including NAT1, mainly carried out HONH-PhIP bioactivation to form N-acetoxy-PhIP, which binds to DNA. (bvsalud.org)
  • 24. Wolfrum C, Spener F. Chlorophyll-derived fatty acids regulate expression of lipid metabolizing enzymes in liver, a nutritional opportunity[J]. OCL - Oleagineux Corps Gras Lipides, 2001, 8(1):39-44. (boysandgirlsclubofcypress.com)
  • Increases bile flow, reduces liver enzymes SGOT and SGPT, prevents and dissolves gall stones. (chineseherbinfo.com)
  • This study highlights the potent antioxidant properties of TD which contribute to its therapeutic effect in AFB 1 -induced HCC in rats. (hindawi.com)
  • 5,9-Dimethyldibenzo[c,g]carbazole (DMDBC), a potent mouse hepatocarcinogen, has been shown to induce a non-linear increase in mutant frequency in the liver of the transgenic MutaMouse. (shengsci.com)
  • Given the high mutagenicity of dG-N 2 -tamoxifen adducts, if not excised, they may potentially contribute to the initiation of endometrial cancer in women. (mssm.edu)
  • Ovarian cancer stem cells that reside within the tumor play a role in cancer recurrence and progression. (biomedres.us)
  • Exposure to 2-nitrotoluene has also been associated with non-cancer effects in experimental animals, including developmental and reproductive effects as well as effects in the lungs, liver, spleen, bone marrow and the hematopoietic system. (gc.ca)
  • Various exposure-selective cross sectional epidemiological studies that look at OHPrVal adducts and cytogenetic effects would be useful. (cdc.gov)
  • Scientists are hopeful that SCC supplementation will be helpful in decreasing the risk of liver cancer in high-risk populations with unavoidable, dietary aflatoxin exposure. (oregonstate.edu)
  • Following exposure to an initial, single dose of 4NQ0, the time course of DNA repair synthesis (as measured by ³HTdR incorporation) was determined. (ndltd.org)
  • 6-7 Many of these lethal side effects, plus recurrence of the original tumor, can happen after the "five-year survival" milestone has been achieved. (lifeextension.com)
  • Various factors have been implicated as risk factors in the pathogenesis of liver cancer, notably food contaminated with aflatoxins, toxins produced by fungi of the genus Aspergillus sp. (hindawi.com)
  • AFB 1 acts as a strong hepatotoxicant, mutagen and naturally occurring hepatocarcinogen, which cause liver cancer in a dose-dependent manner [ 5 ]. (hindawi.com)
  • Your gift will help support our mission to end cancer and make a difference in the lives of our patients. (mdanderson.org)
  • Objective response was defined as TE3/4, and poor TE as TE1/2, evaluated by response evaluation criteria in cancer of the liver at 1-4 months after the procedure. (springeropen.com)
  • On June 25, 2004, the US government proudly announced that 64% of cancer victims are living longer than five years, compared to a 50% five-year survival rate three decades ago. (lifeextension.com)
  • The mortality rate for those diagnosed with head and neck cancer (which does not include brain tumors) is high. (lifeextension.com)
  • Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. (boysandgirlsclubofcypress.com)
  • No tumor-specific expression levels of protein kinase C isoenzymes and of c-fos in human breast cancer cell cultures. (shengsci.com)
  • CYB5A trapped our principal focused not only be induce of lack of knowledge concerning its sub cellular area and down regulation in nuclear membrane of HCC in contrast to fibrotic liver and HepG2 cell lines, but also mainly because of S nitrosylation of this protein. (kspinhibitors.com)
  • Such adducts are responsible for the generation of observable AFB 1 inducible lethal mutation. (hindawi.com)
  • Effects of sodium metallochlorophyllins on the activity and components of the microsomal drug-metabolizing enzyme system in rat liver[J]. Chemical & Pharmaceutical Bulletin, 1986, 34(10):4287-93. (boysandgirlsclubofcypress.com)
  • To this end, the consortium is evaluating about 40 NAs and their capacity to form different types of DNA adducts (i.e., chemical modifications of DNA bases) upon metabolic activation. (fraunhofer.de)
  • pSP189 plasrnid DNA containing the supF gene was treated with α-acetoxytamoxifen and adduct levels (0.5-8.0 adducts per plasmid) determined by 32 P-postlabeling. (mssm.edu)
  • This reactive metabolite escapes from the detoxification process and usually conjugates with DNA nucleotides forming adducts [ 6 ]. (hindawi.com)
  • The standard Ames test is evaluated regarding the impact of the type and amount of solvent and the metabolic activation system (rat versus hamster) on the detection of mutagenic NAs. (fraunhofer.de)
  • Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability. (ucdavis.edu)
  • To evaluate the effects, three end points were employed: DNA repair capacity, cell survival, and chromosome aberrations. (ndltd.org)