This article is a US Government work and, as such, is in the public domain in the United States of America.
Carcinogen–DNA adducts in human breast epithelial cells †
Article first published online: 8 MAR 2002
Copyright © 2002 Wiley-Liss, Inc.
Environmental and Molecular Mutagenesis
Volume 39, Issue 2-3, pages 184–192, 2002
How to Cite
Gorlewska-Roberts, K., Green, B., Fares, M., Ambrosone, C.B. and Kadlubar, F.F. (2002), Carcinogen–DNA adducts in human breast epithelial cells . Environ. Mol. Mutagen., 39: 184–192. doi: 10.1002/em.10060
- Issue published online: 29 MAR 2002
- Article first published online: 8 MAR 2002
- Manuscript Accepted: 29 NOV 2001
- Manuscript Revised: 26 NOV 2001
- Manuscript Received: 21 NOV 2001
- Oak Ridge Institute for Science and Education
- DNA adducts;
- epithelial cells;
- breast milk;
Diet and environmental exposures are often regarded as significant etiologic factors in human breast cancer. Chemicals that may be involved in these exposures include heterocyclic amines, aromatic amines, and polycyclic aromatic hydrocarbons, which also serve as strong mammary carcinogens in different animal models. In this study, we chose to quantify the major DNA adducts derived from one member of each of these classes of carcinogens, that is, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 4-aminobiphenyl (ABP), and benzo[a]pyrene (B[a]P), respectively, in DNA isolated from exfoliated ductal epithelial cells in human breast milk. Milk was collected from healthy, nonsmoking mothers. The isolated DNA was digested to 3′ nucleotides and subjected to 32P-postlabeling. Adduct enrichment was achieved using Oasis Sep-Paks and the analyses were conducted by HPLC using radiometric detection. Critical to the analyses were the syntheses of bis(phosphate) standards for the C8-dG adducts of PhIP and ABP, and the N2-dG adduct of B[a]P, which were added to each reaction as UV markers. Of the 64 samples analyzed, adducts were found in 31 samples. Thirty samples contained detectable levels of PhIP adducts, with a mean value of 4.7 adducts/107 nucleotides; 18 were positive for ABP adducts with a mean value of 4.7 adducts/107 nucleotides; and 13 were found to contain B[a]P adducts with a mean level of 1.9 adducts/107 nucleotides. These data indicate that women are exposed to several classes of dietary and environmental carcinogens and that these carcinogens react with DNA in breast ductal epithelial cells, the cells from which most breast cancers arise. Environ. Mol. Mutagen. 39:184–192, 2002. Published 2002 Wiley-Liss, Inc.