| Effects of Pesticides on the Ratio of 16a/2-Hydroxyestrone: A Biologic Marker of Breast Cancer Risk H. Leon Bradlow,1 Devra Lee Davis,2 Gong Lin,1 Daniel Sepkovic,1 and Raj Tiwari1 1Strang-Cornell Cancer Research Laboratory, New York, New York;
2Office of the Assistant Secretary for Health, Department of Health and Human Services, Washington, DC Abstract
Xenobiotic estrogens are external compounds with estrogenic activity that may thereby affect the risk of breast cancer. This paper describes a mechanism by which xenoestrogens may affect the development of breast cancer. Estradiol metabolism proceeds by hydroxylation at one of two mutually exclusive sites at C-2 and C-16 . The catechol pathway yields the weakly estrogenic 2-hydroxyestrone (2-OHE1) , which inhibits breast cell proliferation. In contrast, the alternative pathway yields the genotoxic 16-hydroxyestrone (16-OHE1) , which enhances breast cell growth, increases unscheduled DNA synthesis, and oncogene and virus expression, and increases anchorage-independent growth. Using a radiometric assay that measures the relative formation of 16-OHE1 versus 2-OHE1 from specifically tritiated estradiol in (ER+) MCF-7 cells, we compared the ratio of 16-OHE1/2-OHE1 observed after treatment with the known rodent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) with the ratios after treatment with DDT, atrazine,  -benzene hexachloride, kepone, coplanar PCBs, endosulfans I and II, linoleic and eicosapentenoic acids, and indole-3-carbinol (I3C) . These pesticides significantly increase the ratio of 16-OHE1/2-OHE1 metabolites to values comparable to or greater than those observed after DMBA. In contrast, the antitumor agent I3C increased 2-OHE1 formation and yielded ratios that are 1/3 of those found in unexposed control cells and 1/10th of those found in DMBA-treated cells. Thus the ratio of 16-OHE1/2-OHE1 may provide a marker for the risk of breast cancer. Assays of this ratio, which can be measured in spot urines, may prove useful for a variety of in vitro and in vivo studies bearing on breast cancer risk. -- Environ Health Perspect 103(Suppl 7) :147-150 (1995) Key words: estrogens, P450 hydroxylation, pesticides, cancer risk, hydroxyestrogens
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