Carcinogenic nitrosamine that may be formed from preservatives in meats during their preparation or in the liver during metabolism.

Oxidative damage and induced mutations in m13mp2 phage DNA exposed to N-nitrosopyrrolidine with UVA radiation. (1/22)

N:-Nitrosopyrrolidine (NPYR) is carcinogenic in rodents and undergoes alpha-hydroxylation upon microsomal CYP450 metabolism, giving rise to mutations. Previously, we reported the direct mutagenicity of NPYR, under ultraviolet A (UVA) irradiation, towards Salmonella typhimurium and phage M13mp2. In the present study, we measured the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in a replicative form of M13mp2 DNA exposed to NPYR plus UVA. Formation of 5-hydroxy-2'-deoxycytidine in calf thymus DNA treated with NPYR plus UVA was also observed. Singlet oxygen is likely to account for the formation of 8-oxodGuo. We analyzed the spectrum of mutations in lacZalpha of M13mp2 phages produced on transfecting Escherichia coli with the replicative form of phage DNA that had been treated with NPYR plus UVA. The role of oxidative DNA damage in mutagenesis was explored using mutM-proficient and -deficient E.coli strains as the hosts. A higher level of mutation was observed with the mutM-deficient host than with the -proficient host. Base substitutions at GC pairs predominated in both mutM-proficient and -deficient hosts. With the mutM-deficient host, we observed an overall increase in the percentage of GC-->TA transversions. In addition we noted that there were fewer GC-->AT transitions than in the mutM-proficient host. With these hosts, different hot spots were observed and a new GC-->TA hot spot was produced. The formation of 8-oxodGuo in DNA, which is known to induce GC-->TA transversion, may contribute to mutagenesis by NPYR plus UVA.  (+info)

Comparative metabolism of N-nitrosopiperidine and N-nitrosopyrrolidine by rat liver and esophageal microsomes and cytochrome P450 2A3. (2/22)

N-nitrosopiperidine (NPIP) is a potent esophageal carcinogen in rats whereas structurally similar N-nitrosopyrrolidine (NPYR) induces liver, but not esophageal tumors. NPIP is a possible causative agent for human esophageal cancer. Our goal is to explain mechanistically these differing carcinogenic activities in the esophagus. We hypothesize that differences in metabolic activation of these nitrosamines could be one factor accounting for their differing carcinogenicity. alpha-Hydroxylation is the key metabolic activation pathway leading to nitrosamine-induced carcinogenesis. In this study, we examined the alpha-hydroxylation rates of [3,4-(3)H]NPIP and [3,4-(3)H]NPYR by male F344 rat esophageal and liver microsomes. The major alpha-hydroxylation products of NPIP and NPYR, 2-hydroxytetrahydro-2H-pyran (2-OH-THP) and 2-hydroxytetrahydrofuran (2-OH-THF), respectively, were monitored by high performance liquid chromatography with radioflow detection. NPIP or NPYR (4 microM) was incubated with varying concentrations of esophageal microsomes and co-factors. Microsomes converted NPIP to 2-OH-THP with a 40-fold higher velocity than NPYR to 2-OH-THF. Similar results were observed in studies with NPIP and NPYR at substrate concentrations between 4 and 100 micro M. Kinetics of NPIP alpha-hydroxylation were biphasic; K(M) values were 312 +/- 50 and 1600 +/- 312 microM. Expressed cytochrome P450 2A3, found in low levels in rat esophagus, was a good catalyst of NPIP alpha-hydroxylation (K(M) = 61.6 +/- 20.5 microM), but a poor catalyst of NPYR alpha-hydroxylation (K(m) = 1198 +/- 308 micro M). Cytochrome P450 2A3 may play a role in the preferential activation of NPIP observed in rat esophagus. Liver microsomes metabolized NPYR to 2-OH-THF (V(max)/K(M) = 3.23 pmol/min/mg/ microM) as efficiently as NPIP to 2-OH-THP (V(max)/K(M) = 3.80-4.61 pmol/min/mg/ microM). We conclude that rat esophageal microsomes activate NPIP but not NPYR whereas rat liver microsomes activate NPIP and NPYR. These results are consistent with previous findings that tissue-specific activation of nitrosamines contributes to tissue-specific tumor formation.  (+info)

Identification of adducts formed in the reaction of alpha-acetoxy-N-nitrosopyrrolidine with deoxyribonucleosides and DNA. (3/22)

N-Nitrosopyrrolidine (NPYR) is a well-established hepatocarcinogen in the rat. NPYR requires metabolic activation by cytochrome P450-catalyzed alpha-hydroxylation to express its carcinogenic activity. This produces alpha-hydroxyNPYR (2), which spontaneously ring opens to 4-oxobutanediazohydroxide (4), a highly reactive intermediate, which may itself modify DNA or yield a cascade of electrophiles that react with DNA to produce adducts. Multiple dGuo adducts formed in this reaction have been previously characterized, but there are no examples of adducts formed with other DNA nucleobases. In this study, we used alpha-acetoxyNPYR (3) as a stable precursor to 2 and 4. Compound 3 was allowed to react with DNA. The DNA was enzymatically hydrolyzed to deoxyribonucleosides, and the products were analyzed by LC-ESI-MS and LC-ESI-MS/MS. Reactions of 3 with individual deoxyribonucleosides were also carried out. The products were identified by their MS, UV, and NMR spectra as N6-(tetrahydrofuran-2-yl)dAdo (16) and N4-(tetrahydrofuran-2-yl)dCyd (17) in addition to the previously characterized N2-(tetrahydrofuran-2-yl)dGuo (13). Unstable dThd adducts were also formed. Further characterization of the adducts was achieved by NaBH3CN reduction of the reaction mixtures of 3 with deoxyribonucleosides or DNA. This produced N6-(4-hydroxybut-1-yl)dAdo (21), N4-(4-hydroxybut-1-yl)dCyd (22), O2-(4-hydroxybut-1-yl)dThd (23), O4-(4-hydroxybut-1-yl)dThd (24), and 3-(4-hydroxybut-1-yl)dThd (25). Adducts 21 and 22 were characterized by their spectral properties, while the dThd adducts 23-25 were identified by comparison to synthetic standards. The results of this study demonstrate that 3 forms adducts with dAdo, dCyd, and dThd in DNA, in addition to the previously characterized dGuo adducts. These newly characterized standards can be used to investigate DNA adduct formation in rats treated with NPYR.  (+info)

Analysis of adducts in hepatic DNA of rats treated with N-nitrosopyrrolidine. (4/22)

N-Nitrosopyrrolidine (NPYR) is a hepatocarcinogen in rats. It is metabolically activated by cytochrome P450 enzymes in the liver leading to the formation of 4-oxobutanediazohydroxide (4) and related intermediates that react with DNA to form adducts. Because DNA adducts are thought to be critical in carcinogenesis by NPYR, we analyzed hepatic DNA of NPYR-treated rats for several adducts: N2-(tetrahydrofuran-1-yl)dGuo (N2-THF-dGuo, 13), N6-THF-dAdo (14), N4-THF-dCyd (17), and dThd adducts 15 and 16. The rats were treated with NPYR in the drinking water, 600 ppm for 1 week, or 200 ppm for 4 or 13 weeks. Hepatic DNA was isolated, enzymatically hydrolyzed, and analyzed by capillary LC-ESI-MS-SIM, which indicated the presence of adducts 13, 14, and 17. Because these adducts can be unstable at the deoxyribonucleoside level, further analyses were carried out using DNA treated with NaBH3CN, which converts adducts 13-17 to N2-(4-hydroxybut-1-yl)dGuo [N2-(4-HOB)dGuo, 18], N6-(4-HOB)dAdo (19), O2-(4-HOB)dThd (20), O4-(4-HOB)dThd (21), and N4-(4-HOB)dCyd (22). [15N]-Labeled analogues of adducts 18-20 and 22 were synthesized and used in this analysis, which was performed by capillary LC-ESI-MS/MS-SRM. Convincing evidence for the presence of adducts 18-22 was obtained. Levels of 18, 19, 20, and 21 were (mumol/mol dGuo): 3.41-5.39, 0.02-0.04, 2.56-3.87, and 2.28-5.05, respectively. Compound 22 was not quantified due to interfering peaks. These results provide the first evidence for tetrahydrofuranyl-substituted DNA adducts in the livers of rats treated with NPYR. The finding of dAdo and dThd adducts is of particular interest since previous studies have shown that NPYR causes mutations at AT base pairs in DNA of rat liver.  (+info)

Chronic nitrosamine ingestion in 1040 rodents: the effect of the choice of nitrosamine, the species studied, and the age of starting exposure. (5/22)

In parallel with a larger experiment on 4080 rats fed 16 different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA) from 6 weeks of age, a variety of smaller experiments on a total of 1040 rodents were undertaken and are the subject of the present report. Three separate subjects were addressed. Studies of 16 different concentrations of N-nitrosopyrrolidine and N-nitrosopiperidine given from age 6 weeks onwards to small groups of rats yielded dose-response relationships for the effects of N-nitrosopyrrolidine on liver tumors and for those of N-nitrosopiperidine on tumors of the liver and upper gastrointestinal tract that resembled those seen for NDMA and NDEA, respectively, except that N-nitrosopyrrolidine and N-nitrosopiperidine were less potent [the respective dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment being approximately 0.4 (males) and 0.6 (females) mg/kg adult body weight/day for each agent]. Alternatively, it was estimated that the risks to rats from lifelong exposure to 1 microgram/kg adult body weight/day of each agent might be about 0.1%, and that the risks to rats from lower doses would be proportionately less. Studies of 16 different concentrations of NDEA on small groups of female mice and female hamsters yielded the types of dose response that would be expected for upper gastrointestinal tumors, liver cell tumors, and Kupffer cell tumors in mice (no other types of liver tumor being produced, in contrast with previous reports) and for tracheal and liver cell tumors in hamsters (no clear effect on upper gastrointestinal tumors being apparent in hamsters). The dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment were approximately 0.3 mg/kg adult body weight/day, i.e., 5 times that for the same agent in rats. In part, however, this may be because treatment started at an older age in these species. Studies were undertaken of the effects on esophageal and liver tumorigenesis of starting the treatment of rats with NDEA at 3 or at 20 weeks of age instead of at 6 weeks of age (as in the main experiment). Earlier treatment resulted in slightly greater dosage rates, if dosage was measured in mg/kg/day, and hence in a correspondingly more rapid yield of esophageal tumors, but the effect was not large. By contrast, an earlier start to treatment resulted, after a fixed duration of treatment, in animals having a 3-fold higher incidence rate of liver tumors, while a later start resulted in a 2-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)  (+info)

Mass spectrometric analysis of a cyclic 7,8-butanoguanine adduct of N-nitrosopyrrolidine: comparison to other N-nitrosopyrrolidine adducts in rat hepatic DNA. (6/22)

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Evolution of research on the DNA adduct chemistry of N-nitrosopyrrolidine and related aldehydes. (7/22)

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The enhancing effect of ethanol on the mutagenic activation of N-nitrosomethylbenzylamine by cytochrome P450 2A in the rat oesophagus. (8/22)

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N-Nitrosopyrrolidine (NPYR) is a chemical compound that falls under the category of nitrosamines. Nitrosamines are potent carcinogens, and NPYR is no exception. It is formed when nitrites, which can be found in certain foods or used as preservatives, come into contact with secondary amines in the digestive system. NPYR has been shown to cause cancer in various animal models, particularly in the liver and pancreas. However, its carcinogenic effects in humans are still a subject of ongoing research.

... n-nitrosopyrrolidine MeSH D03.383.773.700 - pentolinium tartrate MeSH D03.383.773.728 - procyclidine MeSH D03.383.773.812 - ...
... n-nitrosopyrrolidine MeSH D02.654.567.400 - methylnitronitrosoguanidine MeSH D02.654.692.247 - carmustine MeSH D02.654.692.300 ...
... propionitrile N-Nitrosomethylethylamine N-Nitrosomethylvinylamine N-Nitrosomorpholine N-Nitrosopiperidine N-Nitrosopyrrolidine ...
N-nitrosopyrrolidine and in rats treated with the hepatocarcinogen N-nitrosopyrrolidine. Esterase-catalyzed hydrolysis of α- ... Esterase-catalyzed hydrolysis of α-acetoxy-N-nitrosopyrrolidine in the presence of DNA also produced the exocyclic 1,N2- ... Detection of Exocyclic Guanine Adducts in Hydrolysates of Hepatic DNA of Rats Treated with N-Nitrosopyrrolidine and in Calf ... Neutral thermal hydrolysates of hepatic DNA isolated from rats treated with N-nitrosopyrrolidine contained a fluorescent adduct ...
α-Hydroxylation of the Carcinogens N-Nitrosopyrrolidine and N-Nitrosonornicotine. / Hecht, Stephen S.; Chen, Chi hong B. In: ... α-Hydroxylation of the Carcinogens N-Nitrosopyrrolidine and N-Nitrosonornicotine. Journal of Organic Chemistry, 44(9), 1563- ... α-Hydroxylation of the Carcinogens N-Nitrosopyrrolidine and N-Nitrosonornicotine, Journal of Organic Chemistry, vol. 44, no. ... α-Hydroxylation of the Carcinogens N-Nitrosopyrrolidine and N-Nitrosonornicotine. Journal of Organic Chemistry. 1979 Jan 1;44( ...
URXNPYR - N-Nitrosopyrrolidine (NPYR) (ng/L). Variable Name: URXNPYR. SAS Label: N-Nitrosopyrrolidine (NPYR) (ng/L). English ... N-Nitrosopyrrolidine (NPYR) (ng/L). Target: Both males and females 18 YEARS - 150 YEARS. Code or Value. Value Description. ... N-Nitrosopyrrolidine (NPYR) Comment Code. Target: Both males and females 18 YEARS - 150 YEARS. Code or Value. Value Description ...
This page provides lists of substances and exposures that are known or suspected to cause cancer. To help put these lists into context, some related information is included on how different agencies and groups test and classify possible carcinogens.
N-Nitrosopyrrolidine. *N-Nitrososarcosine. *Nitrosourea Chemotherapeutic Agents *Bis(chloroethyl) Nitrosourea. *1-(2- ...
3. Inhibitors of differentiation-1 promotes nitrosopyrrolidine-induced transformation of HPV 16-immortalized cervical ...
As an example of a false positive, we identified "N-Nitrosopyrrolidine" as a blood chemical in one paper (Tan-ariya et al. 1998 ...
... n-nitrosopyrrolidine MeSH D03.383.773.700 - pentolinium tartrate MeSH D03.383.773.728 - procyclidine MeSH D03.383.773.812 - ...
N-nitrosopyrrolidine (Npyr). Nathan Mantel Papers, MS C 610. Archives and Modern Manuscripts Collection. ... N-nitrosopyrrolidine (Npyr). Nathan Mantel Papers, MS C 610. Archives and Modern Manuscripts Collection. https://findingaids. ...
ALPHA-ACETOXY-N-NITROSOPYRROLIDINE (1 supplier). IUPAC Name: (1-nitrosopyrrolidin-2-yl) acetate , CAS Registry Number: 59435-85 ... Synonyms: alpha-Acetoxynitrosopyrrolidine, 1-nitrosopyrrolidin-2-yl acetate, alpha-Acetoxy-N-nitrosopyrrolidine, N-Nitroso-( ...
N Nitrosopyrrolidine use N-Nitrosopyrrolidine n Octanol use 1-Octanol n Octyl Alcohol use 1-Octanol ...
N-Nitrosopyrrolidine Preferred Term Term UI T027561. Date01/01/1999. LexicalTag NON. ThesaurusID ... N-Nitrosopyrrolidine Preferred Concept UI. M0014402. Registry Number. SZ4J5WK201. Related Numbers. 930-55-2. Scope Note. ... N-Nitrosopyrrolidine. Tree Number(s). D02.654.442.550. D03.383.773.630. Unique ID. D009242. RDF Unique Identifier. http://id. ...
N-Nitrosopyrrolidine Preferred Term Term UI T027561. Date01/01/1999. LexicalTag NON. ThesaurusID ... N-Nitrosopyrrolidine Preferred Concept UI. M0014402. Registry Number. SZ4J5WK201. Related Numbers. 930-55-2. Scope Note. ... N-Nitrosopyrrolidine. Tree Number(s). D02.654.442.550. D03.383.773.630. Unique ID. D009242. RDF Unique Identifier. http://id. ...
N-Nitrosopyrrolidine. *N-Nitrososarcosine. *Nitrosourea Chemotherapeutic Agents *Bis(chloroethyl) Nitrosourea. *1-(2- ...
N Nitrosopyrrolidine use N-Nitrosopyrrolidine n Octanol use 1-Octanol n Octyl Alcohol use 1-Octanol ...
Nitrosopyrrolidine 5. Nitrosopiperidine Epoxides, peroxy compounds, and lactones: lL. Epoxides 2. Peroxides 3. Lactones a. g- ...
N-Nitrosopyrrolidine (0) * Pentolinium Tartrate (0) * Procyclidine (0) * Pyrrolidinones (21) * Cotinine (21) ...
... methyl 1-nitrosopyrrolidine-2-carboxylate. Find out PRICE, STOCK, Lead Time & shipping of Vildagliptin N-Nitroso-L-Proline ... methyl 1-nitrosopyrrolidine-2-carboxylate. This product can be used as a working standard or secondary reference standard ( ...
N-Nitrosopyrrolidine. *n-Pentanal. *n-Pentane. *n-Pentanol. *N-Phenyl-2-naphthylamine ...
C44420 X656TZ86DX N-NITROSONORNICOTINE C44414 6N066XUL4L N-NITROSOPIPERIDINE C44423 SZ4J5WK201 N-NITROSOPYRROLIDINE C44424 ...
This graph shows the total number of publications written about "Nafoxidine" by people in this website by year, and whether "Nafoxidine" was a major or minor topic of these publications ...
N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine, and N-nitrosothiazolidine (NTHZ). ...
N-Nitrosopyrrolidine,N-Nitrososarcosine,o-Nitrotoluene,Nitrous oxide, Norethisterone (Norethindrone) ,Norethisterone ( ...
  • The results indicated that the XAD-4 hydrophilic fraction, with normalized yields of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), and N-nitrosopiperidine (NPIP) of 27.2, 5.2, 5.9, and 6.1ng/mg-DOC, respectively, tended to form more N-nitrosamines than the hydrophobic and the transphilic fractions. (psu.edu)
  • The dissociations of α-hydroxy- N -nitrosopyrrolidine, 1 , and α-hydroxy- N -nitrosopiperidine, 2 , to form the nitrosiminium ions, 3 and 4 , respectively, have been studied as models for the S N 1 process of the corresponding α-acetoxy- N -nitrosamines. (mst.edu)
  • The use of RE/GTE had no significant effect on nitrosodiethylamine, nitrosodimethylamine, nitrosopiperidine and nitrosopyrrolidine. (vetdergikafkas.org)
  • This report describes the isolation and characterization of DNA adducts formed in vitro from α-acetoxy- N -nitrosopyrrolidine and in rats treated with the hepatocarcinogen N -nitrosopyrrolidine. (aacrjournals.org)
  • Esterase-catalyzed hydrolysis of α-acetoxy- N -nitrosopyrrolidine in the presence of calf thymus DNA, followed by neutral thermal hydrolysis of the DNA, resulted in formation of three previously unknown Adducts 1-3. (aacrjournals.org)
  • Esterase-catalyzed hydrolysis of α-acetoxy- N -nitrosopyrrolidine in the presence of DNA also produced the exocyclic 1, N 2 -propanodeoxyguanosine Adducts 4 a and 4 b which we have previously described. (aacrjournals.org)