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EVIDENCE FOR THE PRESENCE OF MUTAGENIC ARYL AMINES IN HUMAN BREAST MILK AND DNA ADDUCTS IN EXFOLIATED BREAST-DUCT EPITHELIAL CELLS
Citation:
Thompson, P. A., D M. DeMarini, F. F. Kadlubar, G. Y. McClure, L R. Brooks, B. L. Green, M. Y. Fares, A. Stone, P. D. Josephy, AND C. B. Ambrosone. EVIDENCE FOR THE PRESENCE OF MUTAGENIC ARYL AMINES IN HUMAN BREAST MILK AND DNA ADDUCTS IN EXFOLIATED BREAST-DUCT EPITHELIAL CELLS. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS. Alan R Liss, Inc, New York, NY, 39(2-3):134-142, (2001).
Description:
Aromatic (AA) and heterocyclic amines (HAA) are ubiquitous environmental mutagens present in combustions emissions, fried meats, tobacco smoke, etc., and are suspect human mammary carcinogens. To determine the presence of aryl amines in breast tissue and fluid, we examined exfoliated breast-duct epithelial cells for DNA adducts and for mutagenicity in matched human milk samples. Breast milk was obtained from 50 women who were 4-6 weeks postpartum, and exfoliated epithelial-cell DNA was evaluated for bulky, non-polar DNA adducts by 32P-postlabeling and thin-layer chromatography (TLC). Milk was processed by acid hydrolysis, and the extracted organics were examined in the standard plate-incorporation Ames Salmonella assay using primarily strain YG1024, a strain that detects frameshift mutations and over-expresses arylamine N-acetyltansferase. DNA adducts were identified in 66% of the specimens, and bulky adducts appeared to migrate 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) were positive for mutagenic activity. No correlation was observed between adduct levels in the breast cells and mutagenic activity in the milk. 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) the basic fractions but in only 33% (2/6) of acid samples, indicating that the mutagens were basic compounds, such as aryl amines. Although pilot in nature, this study (a) corroborates previous findings of significant levels of DNA adducts in breast tissue and mutagenicity in human breast milk and (b) indicates that breast-milk mutagens may be moderately polar basic compounds, such as aryl amines.