Inhibition of gap junctional intercellular communication in normal human breast epithelial cells after treatment with pesticides, PCBs, and PBBs, alone or in mixtures.
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.
Kang
K S
KS
Department of Pediatrics/Human Development, Michigan State University, East Lansing, MI 48824, USA.
Wilson
M R
MR
Hayashi
T
T
Chang
C C
CC
Trosko
J E
JE
D001940:Breast / Q000166:cytology*; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D005260:Female; D005618:Fresh Water; D006114:Great Lakes Region; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D010575:Pesticides / Q000633:toxicity; D011075:Polybrominated Biphenyls / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D010575:Pesticides; D011075:Polybrominated Biphenyls; D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls