| Endosulfan, known for its persistence in the environment, is the last cyclodiene pesticide in widespread use. Endosulfan ({dollar}alpha{dollar} and {dollar}beta{dollar} isomers) and its known microbial transformation products were tested for androgen-receptor binding affinity in a cell-free in vitro binding assay using cytosolic prostate tissue extract from mature rats and ({dollar}sp3{dollar}H) R1881 (methyltrienolone), a synthetic androgen. Endosulfan lactone was shown to inhibit binding of androgen to the androgen-receptor. The estrogenic potential of the same compounds was investigated using in vitro cell proliferation studies with the MCF-7 estrogen responsive human breast cancer cell line. Estrogenicity was further investigated by measuring estrogen response element/luciferase reporter gene expression in transiently transfected MCF-7 cells. Endosulfan ({dollar}alpha{dollar} and {dollar}beta{dollar} isomers) and endosulfan diol were shown to possess estrogenic activity in both assays, with endosulfan diol exhibiting greater estrogenic activity than the parent compounds. |
