DNA-damaging activity in vivo and bacterial mutagenicity of sixteen aromatic amines and azo-derivatives, as related quantitatively to their carcinogenicity

Parodi, Silvio; Taningher, Maurizio; Russo, Patrizia; Pala, Mauro; Tamaro, M.; Monti‐Bragadin, C.

doi:10.1093/carcin/2.12.1317

Cited by 122 publications

(85 citation statements)

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“…In the Ames Salmonella strains, 4-ABP and 2-naphthylamine are 2-to 10-fold more mutagenic at the base-substitution allele than at the frameshift allele, whereas the other AAs are more mutagenic at the frameshift allele [Parodi et al, 1981;Levine et al, 1994]. Both HAAs and the AAs are chemically basic; thus, basic extracts of milk were evaluated for mutagenicity in frameshift (YG1024) and base-substitution (YG1029) strains of Salmonella.…”

Section: Human Breast Milk Mutagenicitymentioning

confidence: 99%

Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells

Thompson

DeMarini

Kadlubar

et al. 2002

Environ and Mol Mutagen

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Aromatic and heterocyclic amines are ubiquitous environmental mutagens present in combustion emissions, fried meats, and tobacco smoke, and are suspect human mammary carcinogens. To determine the presence of arylamines in breast tissue and fluid, we examined exfoliated breast ductal epithelial cells for DNA adducts and matched human milk samples for mutagenicity. Breast milk was obtained from 50 women who were 4 -6 weeks postpartum, and exfoliated epithelial-cell DNA was evaluated for bulky, nonpolar DNA adducts by 32 P-postlabeling and thin-layer chromatography. Milk was processed by acid hydrolysis, and the extracted organics were examined in the standard plate-incorporation Ames Salmonella assay using primarily strain YG1024, which detects frameshift mutations and overexpresses aryl amine N-acetyltransferase. DNA adducts were identified in 66% of the specimens, and bulky adducts migrated in a pattern similar to that of 4-aminobiphenyl standards. The distribution of adducts did not vary by NAT2 genotype status. Of whole milk samples, 88% (22/25) had mutagenic activity.Among the samples for which we had both DNA adduct and mutagenicity data, 58% (14/19) of the samples with adducts were also mutagenic, and 85% (11/13) of the mutagenic samples had adducts. Quantitatively, no correlation was observed between the levels of adducts and the levels of mutagenicity. Separation of the milk showed that mutagenic activity was found in 69% of skimmed milk samples but in only 29% of the corresponding milk fat samples, suggesting that the breast milk mutagens were moderately polar molecules. Chemical fractionation showed that mutagenic activity was found in 67% (4/6) of the basic fractions but in only 33% (2/6) of acidic samples, indicating that the mutagens were primarily basic compounds, such as arylamines. Although pilot in nature, this study corroborates previous findings of significant levels of DNA adducts in breast tissue and mutagenicity in human breast milk and indicates that breast milk mutagens may be moderately polar basic compounds, such as arylamines.

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Section: Human Breast Milk Mutagenicitymentioning

confidence: 99%

Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells

Thompson

DeMarini

Kadlubar

et al. 2002

Environ and Mol Mutagen

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“…Widely occurring dietary nitrosatable cornpounds are amines, amides, guanidines and ureas. Hydrazine derivatives could not be included in the study, first because no information on their kinetics of nitrosation was available and secondly because many hydrazine compounds are known to possess mutagenic and carcinogenic activity in their own right, without requiring prior nitrosation (Kimball, 1977;Parodi et al 1981). The remaining compounds, while synthesized industrially, are not known to be natural dietary constituents and were therefore not included in this risk assessment.…”

mentioning

confidence: 99%

Assessment of the risk of formation of carcinogenic N-nitroso compounds from dietary precursors in the stomach

Shephard

Schlatter

Lutz

1987

Food and Chemical Toxicology

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Summary-A Iiterature review has shown that the daily intakes of various N -nitroso-precursor classes in a typical European diet span five orders of magnitude. Amides in the form of protein, and guanidines in the form of creatine and creatinine, are the nitrosatable groups found most abundantly in the diet, approaching Ievels of 100 g/day and 1 gjday, respectively. Approximately 100 mg of primary amines and amino acids are consumed daily, whereas aryl amines, secondary amines and ureas appear to lie in the 1-10 mg range. The ease of nitrosation of each precursor was estimated, the reactivities being found to span seven orders of magnitude, with ureas at the top and amines at the bottom of the scale. From this infonnation and an assessment of the carcinogenicity of the resulting N-nitroso derivatives, the potential health risk due to gastric in vivo nitrosation was calculated. The combined effects of these risk variables were analysed using a simple mathematical model: Risk = [daily intake of precursor] x [gastric concen· tration of nitrite]" x [nitrosatability rate constant} x [carcinogenicity of derivative]. The risk estimates for the various dietary components spanned nine orders of magnitude. Dietary ureas and aromatic amines combined with a high nitrite burden could pose as great a risk as the intake of preformed dimethylnitrosamine in the diet. In contrast, the risk posed by the in vivo nitrosation of primary and secondary amines is probably negligib1y small. The risk contribution by amides (including protein), guanidines and primary amino acids is intermediate between these two extremes. Thus three priorities for future work are a comprehensive study of the sources and Ievels of arylamines and ureas in the diet, determination of the carcinogenic potencies of key nitrosated products to replace the necessarily vague categories used so far, and the development of short-term in situ tests for studying the alkylating power or genotoxicity of N-nitroso compounds too unstable for inclusion in long-term studies.

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“…With the alkaline elution method, significant (p < 0.002) DNA fragmentation was found in the livers of male rats, 4 and 24 hours after intraperitoneal injection of the substance at a dose of 3.64 mmole/kg (c 730 mg/kg) [12]. Other authors [27] using viscometric methods, however, could not demonstrate DNA strand breaks in the liver cells.…”

Section: Genotoxicitymentioning

confidence: 90%

4,4′‐Oxydianiline [MAK Value Documentation, 1993]

2012

The MAK‐Collection for Occupational Health and Safety

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Published in the series Occupational Toxicants , Vol. 6 (1993) The article contains sections titled: Toxic Effects and Modes of Action Pharmacokinetics Effects in Man Effects on Animals Acute toxicity Dermal toxicity Subchronic and chronic toxicity Sensitization tests Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

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DNA-damaging activity in vivo and bacterial mutagenicity of sixteen aromatic amines and azo-derivatives, as related quantitatively to their carcinogenicity

Cited by 122 publications

References 0 publications

Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells

Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells

Assessment of the risk of formation of carcinogenic N-nitroso compounds from dietary precursors in the stomach

4,4′‐Oxydianiline [MAK Value Documentation, 1993]

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