ESTROGENIC PESTICIDES - BINDING RELATIVE TO ESTRADIOL IN MCF-7 CELLS AND EFFECTS OF EXPOSURE DURING FETAL LIFE ON SUBSEQUENT TERRITORIAL BEHAVIOR IN MALE-MICE

Numerous chemicals released into the environment by man are able to di srupt the functioning of the endocrine system by binding to estrogen r eceptors in estrogen-responsive cells. The ability of o,p'-dichlorodip henyl trichloroethane (DDT) and methoxychlor to compete with estradiol for binding to estrogen receptors in MCF-7 cells (relative binding af finity; RBA) was examined in both serum-free medium and 100% serum; th is is referred to as a relative binding affinity-serum modified access (RBA-SMA) assay. RBA's ranged from 0.04% for o,p'-DDT (which showed e nhanced access to cells in serum relative to serum-free medium) to 0.0 04% for methoxychlor (which did not show enhanced access in serum). Ba sed on these findings, these pesticides, along with diethylstilbestrol (DES) as a positive control, were fed to pregnant mice from days 11-1 7 of pregnancy. When the male offspring were examined in adulthood for their rate of urine marking in a novel territory (territorial behavio ur), the rate of urine marking increased dramatically with low doses o f DES (relative to controls) and then decreased significantly at the h ighest dose administered prenatally. Relative binding in MCF-7 cells a ccurately predicted the doses of o,p'-DDT and methoxychlor that produc ed the same results, providing support for the hypothesis that effects on behaviour were mediated by binding to estrogen receptors in the de veloping brain.