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Kyung-Sun Kang,¹ Melinda R. Wilson,¹ Tomonori Hayashi,¹ Chia-Cheng Chang,^1,3 and James E. Trosko^1,2,3

¹Department of Pediatrics/Human Development, ²Institute of Environmental Toxicology, and ³Cancer Center of MSU, Michigan State University, East Lansing, MI 48824 USA

Abstract
Chemical pollutants in the Great Lakes have found their way through the food chain into humans because of their environmental persistence and lipophilicity. Some epidemiological studies have claimed an association between metabolites of 2,2-bis(p-chlorophenyl) -1,1,1-trichloroethane (DDT) , polychlorinated biphenyls (PCBs) , and polybrominated biphenyls (PBBs) and breast cancer, but others have reported no such association. We examined various halogenated hydrocarbons for their capacity to 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 redistribution after photobleaching techniques were used to measure GJIC ; immunostaining and Western and Northern analyses were performed on connexin 43 (Cx43) gap junction protein and message to determine how halogenated hydrocarbons might affect GJIC.

DDT, dieldrin, and toxaphene inhibited GJIC in a dose-responsive manner after 90 min treatments. Dieldrin suppressed GJIC within 30 min with no recovery after 24 hr. Inhibition of GJIC by DDT and toxaphene was partially restored after 12 hr and fully restored after 24 hr. Several PCB and PBB congeners inhibited GJIC in a dose-responsive and time-dependent manner, but GJIC was almost restored to control values 24 hr after exposure. The highest concentrations of the individual chemicals that did not inhibit GJIC was determined, and mixtures containing two of these chemicals were tested for their ability to inhibit GJIC. Significant inhibition of GJIC was observed when cells were treated with a mixture of DDT and 2,4,5-hexachlorobiphenyl (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 the post-translational level. These results are consistent with the hypothesis 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. Key words: chemical mixtures, DDT, dieldrin, gap junctional intercellular communication, normal human breast epithelial cells, PCBs, PBBs, toxaphene. Environ Health Perspect 104:192-200 (1996)

Address correspondence to J.E. Trosko, Department of Pediatrics/Human Development, B240 Life Sciences, Michigan State University, East Lansing, MI 48824 USA.

This research was supported by grants from the Michigan Great Lakes Protection Fund, NIEHS (2942E504911) , and U.S. Air Force Office of Scientific Research (F49620-92-J-0293) , and from a series of Meridian Ultima upgrade instrument grants from the Cancer Center of MSU, College of Human Medicine, MSU Office of Research, and the Provost Office.We acknowledge the discussions and assistance of Diane Matesic, Heather de Feijter-Rupp, and Edwin de Feijter. The word processing skills of Robbyn Davenport and Linda Hartwig are acknowledged.

Received 21 August 1995 ; accepted 20 November 1995.