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C Malaveille

Publications and source records attributed to C Malaveille.

At least 55 records · Page 3Linked to original sources
PubMed1990

32P-postlabelling analysis of DNA adducted with urinary mutagens from smokers of black tobacco.

In order to characterize the tobacco-derived mutagens excreted in the urine of tobacco smokers, 32P-postlabelling techniques were used to examine DNA adducts formed from these mutagens with calf thymus DNA in the presence of a metabolic activation system (rat liver S9, Aroclor 1254-induced, with or without acetyl coenzyme A). Using either nuclease P1 or butanol extraction procedures, four-six and three spots, respectively, were reproducibly found on the autoradiograms in the case of the urine extract from two smokers of black tobacco. Using the urinary extract from a non-smoker, only three faint spots were detected after nuclease P1 enrichment. DNA adducts produced in smokers' urine were then compared with those formed by four N-hydroxyarylamines, N-hydroxy-2-amino-3,8-dimethyl-3H-imidazo[4,5-f]quinoxaline, N-hydroxy-2-amino-3-methyl-imidazo[4,5-f]quinoxaline, N-hydroxy-2-naphthylamine and N-hydroxy-4-aminobiphenyl. Visual inspection revealed that none of the reference aromatic amines contributed to the adduct pattern produced by the urinary mutagen(s). However, primary aromatic amines are mainly implicated as urinary mutagens because: (i) they produce frameshift mutations in Salmonella typhimurium strains, (ii) they are easily extractable with blue cotton and (iii) their mutagenicity is abolished by a nitrite treatment procedure for deamination.

Animals↗
PubMed1990

Contribution of DNA methylation and benzylation to N-nitroso-N-benzyl-methylamine-induced mutagenesis in bacteria: effects of rat liver cytochrome P450 isozymes and glutathione transferases.

The mutagenicity of N-nitroso-N-benzyl-methylamine (NBzMA), N-benzyl-N-nitrosourea (BzNU) and N-methyl-N-nitrosourea (MNU) in Salmonella typhimurium strains was investigated. BzNU selectively mutated TA100 strain as compared to TA1535, whereas MNU showed an inverse strain response, an effect probably related to the fact that benzylation of DNA is a stronger inducer of SOS DNA repair than methylation, as indicated by the higher activity of BzNU in the SOS chromotest. Benzylation of bacterial DNA by NBzMA, as deduced from the differential strain responsiveness, contributed predominantly to its mutagenicity in the presence of liver preparation from untreated, Aroclor- or ethanol-treated rats. Since benzyl alcohol, a metabolite of NBzMA, was not mutagenic in S. typhimurium, it appears that benzyl carbonium cations responsible for the mutagenicity of NBzMA in TA100 are formed via cytochrome P450-mediated hydroxylation of the methyl group. Neither ferric-EDTA nor desferrioxamine altered the mutagenicity of NBzMA, suggesting that activation occurs mainly within the catalytic site of P450. Experiments with isozyme-specific monoclonal antibodies showed that P450IIE1 did not contribute to N-demethylation of NBzMA at either low or high substrate concentrations and that P450IA contributed only weakly. Debenzylation was catalysed predominantly by P450IA at high NBzMA concentration. Antibodies against rat liver P450IIB enhanced NBzMA mutagenicity in S. typhimurium TA1535 strain up to 17-fold at low substrate concentration, but were without effect at high concentration. In liquid incubation assays, a 100% GSH-dependent reduction of NBzMA mutagenicity was found with liver S9 from untreated Wistar rats. The reducing effect of GSH was less pronounced in the presence of liver S9 from BDVI or Fischer 344 rats.

Animals↗
PubMed1990

Screening assays for carcinogenic agents and mixtures: an appraisal based on data in the IARC Monograph series.

To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans and which types of short-term test are more relevant for predicting human hazards, an analysis was performed on agents that were evaluated in IARC Monographs Supplements 6 and 7 for their carcinogenic effects in humans and animals and for activity in short-term genotoxicity tests. The prevalence of genotoxicity among four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 66) was determined. Each of the groups 1, 2A and 2B contained a high proportion (80-90%) of genotoxic carcinogens, which were also multi-species or multi-tissue carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and many in group 3. Although limited by the data-base available through the Monographs series, this analysis implies that genotoxic carcinogens add more to the human cancer burden than non-genotoxic carcinogens. Thus, the continued use of in vitro/in vivo short-term tests, involving as endpoints DNA chromosomal or mutational damage, to identify genotoxic carcinogens or in the isolation of carcinogenic components in complex mixtures is fully justified. It is concluded that (a) an agent or complex mixture with unknown carcinogenic potential showing sufficient evidence of activity in genotoxicity assays in vitro or in vivo is likely to represent a hazard to humans and (b) an agent or complex mixture showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity for rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens.

Animals↗
PubMed1989

Volatile nitrosamine levels and genotoxicity of food samples from high-risk areas for nasopharyngeal carcinoma before and after nitrosation.

Traditional life-style, especially food habits, infection by Epstein-Barr virus (EBV) and genetic factors, have been associated with an increased risk of nasopharyngeal carcinoma (NPC). N-Nitroso compounds and other carcinogens either present in food or formed endogenously, as well as food constituents that activate EBV, have been suspected as etiological factors in NPC pathogenesis. For their characterization preserved food items, frequently consumed in NPC endemic areas in Tunisia, South China and Greenland, were sampled and screened for the presence of mutagens and volatile nitrosamines before and after nitrosation. Aqueous extracts as well as 2 organic extracts of the samples were assayed for genotoxicity in 2 Salmonella typhimurium strains and the SOS chromotest. The same extracts had previously been analyzed for volatile nitrosamines and for EBV-activating substances in Raji cells. In our study, 13 out of 16 food samples showed a weak, directly-acting genotoxicity in the SOS chromotest in at least one of the extracts, but only one sample from Greenland was found to be weakly mutagenic in Salmonella TA 98. Chemical nitrosation for 9 out of 15 samples of aqueous food extracts increased the genotoxic effect in the SOS chromotest. Levels of volatile nitrosamines were also elevated for 12 out of 15 samples; highest levels of N-nitrosodimethylamine were found in hard salted and dried fish from China (1,200 micrograms/kg) and highest N-nitrosopyrrolidine levels in a Tunisian spice (3,840 micrograms/kg). In non-nitrosated aqueous food extracts, the level of volatile nitrosamines and genotoxic activities were not correlated with the EBV-inducing activity of the same samples. After chemical nitrosation, EBV-inducing activity was decreased or showed no change and was not correlated with increases in either the genotoxicity or the nitrosamine levels. Our results suggest that EBV-activating compounds belong to a different class of substances. However, there was an association between the changes in genotoxicity and nitrosamine levels due to nitrosation.

Carcinoma↗
PubMed1989

Prevalence of genotoxic chemicals among animal and human carcinogens evaluated in the IARC Monograph Series.

To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in humans and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and on agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and 3. The results of this analysis indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro/in vivo genotoxicity assays (involving as endpoints DNA damage and chromosomal/mutational damage) may represent a hazard to humans; and b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall, this analysis implies that genotoxic carcinogens add more to the cancer burden in man than non-genotoxic carcinogens. Thus, identification of such genotoxic carcinogens and subsequent lowering of exposure will remain the main goal for primary cancer prevention in man.

Animals↗
PubMed1989

Formation of direct-acting genotoxic substances in nitrosated smoked fish and meat products: identification of simple phenolic precursors and phenyldiazonium ions as reactive products.

Epidemiological studies have associated the consumption of smoked fish and meat products with an increased risk of stomach cancer. Therefore, the reaction of such smoked foods with nitrite under acidic conditions was investigated and was shown to produce potent direct-acting genotoxic substances as detected by the SOS Chromotest. Similar genotoxic activity was observed in nitrosated samples of wood-smoke condensates. Simple phenolic compounds such as phenol, 3-methoxycatechol, catechol and vanillin were identified as the precursors of the genotoxic substances. These phenolic compounds also exhibited direct-acting genotoxicity after nitrosation. The major genotoxic substances formed after nitrosation of phenol were isolated and identified as 4- and 2-hydroxyphenyldiazonium ions. Nitrosation of various wood-smoke condensates was found to generate the same type of diazonium compounds, which in part account for the genotoxicity of nitrosated smoked foods.

Animals↗
PubMed1989

Carcinogenic nitrosamines: free radical aspects of their action.

NDMA and other nitrosamines may be activated into DNA binding intermediates by a cytochrome P450-dependent formation of alpha-nitrosamino radicals or photochemically. Within the catalytic site of cytochrome P450, these radical intermediates either combine with HO. to form alpha-hydroxynitrosamines or decompose into nitric oxide and N-methylformaldimine. In the presence of phosphate, nutagenic alpha-phosphonooxy derivatives are formed from radicals generated chemically/photochemically. Studies on lipid peroxidation, in vivo and in vitro, have further suggested that radicals are formed as intermediates from N-nitrosodialkylamines. The level of nitrosamine-induced lipid peroxidation parallels hepatocarcinogenicity in rats. These data, although preliminary, provide further evidence that free radical damage and DNA alkylation are involved in carcinogenesis induced by nitrosamines.

Animals↗
PubMed1989

Levels of mutagens in the urine of smokers of black and blond tobacco correlate with their risk of bladder cancer.

Levels of urinary mutagens, thioethers, N-nitrosamino acids, nitrate, nicotine, cotinine and creatinine were measured in 21 non-smokers, 26 smokers of blond tobacco, 9 smokers of black tobacco and 5 smokers of both types of tobacco, all eating a similar diet. Results were expressed either per 24 h urine or per mmol creatinine. The sum of urinary nicotine and cotinine levels (N + C) was used as a measure of exposure to the number of cigarettes smoked. Statistically significant positive dose-effect relationships were obtained between the urinary N + C levels and (i) the number of revertants (Salmonella typhimurium TA98, with a metabolic activation system); (ii) the concentration of thioethers; (iii) the levels of N-nitrosoproline or the sum of all nitrosamino acids excreted and (iv) the amount of urinary nitrate. No such correlation was found between N + C levels and induction potency in the SOS chromotest. A linear dose-effect relationship between urinary mutagenicity (i.e. log revertants of S. typhimurium TA98) and N + C levels or number of cigarettes per day was established for smokers of blond tobacco. After adjustment for N + C levels, the urine of smokers of black tobacco contained twice as much mutagenic material as did the urine of blond tobacco smokers (P = 0.02). For other exposure markers, no statistically significant difference was found between the two types of smokers. Epidemiological studies have shown that the risk of urinary bladder cancer is 2.5 times higher in smokers of black tobacco than in blond tobacco. Therefore, our findings on urinary mutagenicity provide experimental evidence that the type of tobacco is the factor responsible for the observed difference in risk and that smoking of black as compared to blond tobacco results in a higher exposure of the urinary bladder to genotoxic hence potentially carcinogenic substances.

Cotinine↗
PubMed1989

[The relation between carcinogenesis and mutagenesis: a re-evaluation].

To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans and which types of short-term tests are more relevant for predicting human hazards, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in human and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxicity among four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 66) was determined. Each of the groups 1, 2A and 2B contained a high proportion (80-90%) of genotoxic carcinogens, which were also multiple-species or multi-tissue carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and many group 3. Although limited by the data-base available through the Monographs Series, this analysis implies that genotoxic carcinogens add more to the human cancer burden than non-genotoxic carcinogens. Thus, the continued use of in vitro/in vivo short-term tests, involving as endpoints DNA chromosomal damage, to identify genotoxic carcinogens or the isolation of carcinogenic components in complex mixtures is fully justified. It is concluded that a) an agent or complex mixture with unknown carcinogenic potential showing sufficient evidence of activity in genotoxicity assays in vitro or in vivo is likely to represent a hazard to humans and b) an agent or complex mixture showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity for rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall one can deduce that identification and subsequent lowering of exposure to genotoxic agents/mixtures will remain one of the main goals for primary cancer prevention in man.

Animals↗
PubMed1989

[Genotoxicity of carcinogenic substances in humans and animals].

To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the I.A.R.C. Monographs for their carcinogenic effects in human and animals and for the activity in short-term tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and of agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. Neither the prevalence of genotoxic carcinogens nor the distribution of carcinogenic potency in rodents reveal any specific characteristics of the human carcinogens in group 1 that differentiates them from agents in groups 2A and 2B or from many in group 3. This suggests that substances in group 2A and 2B and possibly several in group 3, are carcinogenic to humans. These results indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro/in vivo genotoxicity assays (involving as endpoints DNA damage, chromosomal/mutational damage) may represent a hazard to humans; and (b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens.

Animals↗
PubMed1988

Epstein-Barr virus activation in Raji cells by extracts of preserved food from high risk areas for nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) activation of latent infection and traditional life styles, especially food habits, have been strongly associated with an increased risk of nasopharyngeal carcinoma (NPC) in humans. On the basis of anthropological studies in Tunisia, southern China and Greenland, extracts of representative preserved food items consumed frequently by the high-risk populations for NPC were assayed for the presence of EBV activators in Raji cells. A strong EBV activation activity was observed in aqueous extracts of some Cantonese salted dried fish from China, harissa (a spice mixture) and to a lesser extent qaddid (dry mutton preserved in olive oil) from Tunisia. These new data may support epidemiological evidence for the importance of Cantonese salted and dried fish and other food items in the etiology of NPC.

China↗
PubMed1988

Quantification of the genotoxic effects of alkylating agents in bacterial assays.

The genotoxic effects of 11 monofunctional alkylating carcinogens in the Escherichia coli Multitest, SOS Chromotest and Salmonella assay were quantified using the 'yield versus lethal hit plot' method. In this method, the genotoxic yield-potency is defined as the integral under the yield versus lethal hit curve, whereas the genotoxic yield-efficiency is defined as the maximum yield obtained. With the series of substances tested, these two genotoxicity indices were found to be equivalent in the E. coli Multitest. The three bacterial short-term tests were compared and the following observations made: (i) the mutagenic efficiencies in the Salmonella assay and in the Multitest are correlated; (ii) the SOS-inducing efficiency in the SOS Chromotest correlates with both the SOS-inducing efficiency and the recombinogenic efficiency in the Multitest; (iii) mutagenesis and SOS induction measured by the same protocol in the Multitest are clearly distinct phenomena; (iv) when quantified with the 'yield versus lethal hit plot' method, the data from the SOS Chromotest do not correlate any more with the data from the Salmonella assay. Therefore the SOS Chromotest should be considered as a complementary rather than an alternative test to the Salmonella assay. Consequently, the Multitest appears as a relevant candidate for the basis of a battery of tests since it permits the measurement of at least two independent genotoxic effects in a single bacterial system. The method of quantification of genotoxic potencies using the 'yield versus lethal hit plot' method demonstrates the quantitative relationships existing between the data obtained using different systems measuring the same genotoxic effect and differentiates different genotoxic effects from each other.

Alkylating Agents↗
PubMed1987

Synthesis, structure-activity relationships and a reaction mechanism for mutagenic N-nitroso derivatives of glycosylamines and Amadori compounds--model substances for N-nitrosated early Maillard reaction products.

A series of nine glycosylamines and an Amadori compound were synthesized, together with their N-nitroso derivatives. Their structures were established by physico-chemical and spectroscopic data and elemental analyses. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentopyranosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (the Amadori compound) and N-3-ethylindole-D-xylopyranosylamine were shown to be direct-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to depend on the structure of the amine and the sugar moieties and to require the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arenediazonium cations. The formation of these compounds was detected by azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass spectrometric analyses. These data implicate arene(alkyl)diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines (and possibly of N-nitroso Amadori compounds), a little-explored class of N-nitroso compounds that may be formed in vivo.

Amino Sugars↗
PubMed1987

Substituted hydroxyphenanthrenes in opium pyrolysates implicated in oesophageal cancer in Iran: structures and in vitro metabolic activation of a novel class of mutagens.

Previous epidemiological and laboratory studies have indicated an association between the ingestion of opium pyrolysates, dietary deficiencies and the high incidence of oesophageal cancer in subjects in north-east Iran. Pyrolysates of opium, and particularly of morphine, a major opium alkaloid, were both shown to contain similar highly mutagenic substances that were also clastogenic in mammalian cells and which transformed hamster embryo cells in culture. We now report the isolation and characterization of nine of the most abundant mutagenic compounds present in morphine pyrolysates, using h.p.l.c, GC-MS and n.m.r. spectroscopy. The hitherto unknown compounds, all containing a hydroxyphenanthrene moiety, were identified as: I, 3-methyl-3H-naphth[1,2-e]indol-10-ol; II, 1,2-dihydro-3-methyl-3H-naphth[1,2-e]indol-10-ol; III, 1-methyl-1H-naphth[2,1-g]indol-10-ol; IV, 2-methylphenanthro[3,4-d]-[1,3]oxazol-10-ol; V, 6-methylaminophenanthren-3-ol; VI, 2-methyl-3H-phenanthro[3,4-d]imidazol-10-ol; VII, 1,2-dimethyl-1H-phenanthro[3,4-d]imidazol-10-ol; VIII, 2,5-dimethyl-3H-phenanthro[3,4-d]imidazol-10-ol; and IX, 2-ethyl-3H-phenanthro[3,4-d]imidazol-10-ol. Structures for the heterocyclic rings of compounds IV and VI to IX are tentative. Mutagenicity in Salmonella typhimurium TA98 in the presence of rat liver homogenates increased in the order listed and ranged over four orders of magnitude, IX being 1000 times more active than benzo[a]pyrene. Compounds I and VII were converted by rat liver 9000 g supernatant into phenols and dihydrodiols, implicating arene oxides as ultimate mutagens. The formation and reaction of these arene oxides was shown by trapping experiments in vitro with ethanethiol and subsequent characterization of the ethyl sulfide reaction products. The order of biological activity of compounds I-IX, dependent on the structure of the heterocyclic ring, suggests that carbocations, resonance-stabilized as quinone methides, are their ultimate reactive metabolites. Our results lend additional support to the role of opium pyrolysates as an etiological factor in oesophageal cancer in north-east Iran.

Biotransformation↗
PubMed1987

A monoclonal antibody against cytochrome P-450 enhances mutagen activation of N-nitrosodimethylamine by mouse liver S9: studies on the mode of action.

The effect of the monoclonal antibody MAb 2-66-3, directed against the major rat liver phenobarbital (PB)-induced cytochrome P-450 (P-450), on the S9-mediated mutagenicity of N-nitrosodimethylamine (DMN) in Salmonella typhimurium strain TA1530 was studied using liver S9 from PB-treated mice. This MAb enhanced approximately 2-fold S9-mediated mutagenicity of DMN but inhibited both its N-demethylation and N-denitrosation by 50%. Thus MAb-mediated enhancement of DMN mutagenesis does not result from altered activation/inactivation pathways, both known to involve P-450 isozymes. DMSO, a hydroxyl radical (HO.) scavenger and desferrioxamine, an inhibitor of HO.-dependent reactions, quenched the MAb-mediated enhancement of DMN mutagenesis, implicating the HO.-dependent activation of DMN to mutagenic species. As a mechanism, we propose that the binding of this MAb to P-450 isozyme implicated in DMN metabolism decreases the functional coupling between the reductase and the P-450 complex, leading to an increased electron flow from the reductase towards molecular oxygen to form reduced oxygen species (HO.) at the expense of the monooxygenase functions.

Animals↗
PubMed1987

Synthesis, analysis and mutagenic activity of N-nitroso derivatives of glycosylamines and Amadori compounds: nitrosated model substances for the early Maillard reaction products.

A series of nine glycosylamines and an Amadori compound and their N-nitroso derivatives were synthesized. The structures were ascertained by spectroscopy and elemental analysis. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (Amadori compound) and N-3-ethylindole-D-xylosylamine were shown to be directly-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to be dependent on the structure of the amine and the sugar moieties and requires the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arene diazonium cations. Their formation was detected via azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass-spectrometric analyses. Our data implicate arene (alkyl) diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines and N-nitroso Amadori compounds, a little explored class of N-nitroso compounds which may be formed in vivo.

Amino Sugars↗
PubMed1986

Identification, occurrence and mutagenicity in Salmonella typhimurium of two synthetic nitroarenes, musk ambrette and musk xylene, in Indian chewing tobacco and betel quid.

During N-nitrosamine analysis of extracts of betel quid with tobacco and of the saliva of chewers of betel quid with tobacco for N-nitrosamines using a Thermal Energy Analyzer, two unknown compounds were detected. They were identified as synthetic nitro musks, musk ambrette (5-tert-butyl-1,3-dinitro-4-methoxy-2-methylbenzene, CAS No. 83-66-9) and musk xylene, (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene, CAS No. 81-15-2), by gas chromatography-mass spectrometry and Fourier transform nuclear magnetic resonance spectroscopy. These compounds were detected in several samples of betel quid with tobacco and in perfumed tobacco used for chewing in India in amounts ranging from 0.45-23.5 mg/g wet weight. Musk ambrette was found to be mutagenic in Salmonella typhimurium TA100 requiring metabolic activation by rat-liver postmitochondrial supernatant but musk xylene lacked mutagenicity.

Animals↗