This article is a US Government work and, as such, is in the public domain in the United States of America.
Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells †
Article first published online: 7 MAR 2002
Copyright © 2002 Wiley-Liss, Inc.
Environmental and Molecular Mutagenesis
Volume 39, Issue 2-3, pages 134–142, 2002
How to Cite
Thompson, P. A., DeMarini, D. M., Kadlubar, F. F., McClure, G. Y., Brooks, L. R., Green, B. L., Fares, M. Y., Stone, A., Josephy, P. D. and Ambrosone, C. B. (2002), Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells . Environ. Mol. Mutagen., 39: 134–142. doi: 10.1002/em.10067
- Issue published online: 29 MAR 2002
- Article first published online: 7 MAR 2002
- Manuscript Accepted: 29 NOV 2001
- Manuscript Revised: 16 NOV 2001
- Manuscript Received: 10 OCT 2001
- Canadian Breast Cancer Foundation
- DNA adducts;
- Salmonella mutagenicity;
- breast milk;
- aryl amines
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 32P-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. Environ. Mol. Mutagen. 39:134–142, 2002. Published 2002 Wiley-Liss, Inc.