INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN NORMAL HUMAN BREAST EPITHELIAL-CELLS AFTER TREATMENT WITH PESTICIDES, PCBS, ANDPBBS, ALONE OR IN MIXTURES

Chemical pollutants in the Great Lakes have found their way through th e food chain into humans because of their environmental persistence an d lipophilicity. Some epidemiological studies have claimed an associat ion between metabolites of 2,2-bis(p-chlorophenyl)-1,1,1-trichloroetha ne (DDT), polychlorinated biphenyls (PCBs), and polybrominated bipheny ls (PBBs) and breast cancer, but others have reported no such associat ion. We examined various halogenated hydrocarbons for their capacity t o inhibit gap junctional intercellular communication (GJIC) in normal human breast epithelial cells (HBEC) when given as single compounds or as mixtures. The scrape-loading/dye transfer and fluorescent redistri bution after photobleaching techniques were used to measure GJIC; immu nostaining and Western and Northern analyses were performed on connexi n 43 (Cx43) gap junction protein and message to determine how halogena ted hydrocarbons might affect GJIC. DDT, dieldrin, and toxaphene inhib ited GJIC in a dose-responsive manner after 90 min treatments. Dieldri n suppressed GJIC within 30 min with no recovery after 24 hr. inhibiti on of GJIC by DDT and toxaphene was partially restored after 12 hr and Fully restored after 24 hr. Several PCB and PBB congeners inhibited G JIC in a dose-responsive and time-dependent manner, but GJIC was almos t restored to control values 24 hr after exposure. The highest concent rations of the individual chemicals that did not inhibit GJIC was dete rmined, and mixtures containing two of these chemicals were rested for their ability to inhibit GJIC. Significant inhibition of GJIC was obs erved when cells were treated with a mixture of DDT and 2,4,5-hexachlo robiphenyl (2,4,5-HCB), dieldrin and 2,4,5-HCB, or dieldrin and 2,4,5- hexabromobiphenyl (2,4,5-HBB). These results indicate that halogenated hydrocarbons, alone or in specific combinations, can alter GJIC at th e post-translational level. These results are consistent with the hypo thesis that DDT, dieldrin, toxaphene, 2,3,4-HCB, 2,4,5-HCB, and 2,4,5- HBB could have tumor-promoting potential in human breast tissue.