Effects of trichloroethylene and its metabolites on rodent hepatocyte intercellular communication.
Chronic exposure to trichloroethylene (TCE) results in hepatocellular cancer in mice but not rats. The induction of hepatic tumors by TCE appears to be mediated through nongenotoxic or tumor promotion mechanisms. One cellular effect exhibited by a number of nongenotoxic carcinogens and tumor promoters is the inhibition of gap junction mediated intercellular communication. In the present study, the effects of trichloroethylene (TCE) and its metabolites, trichloracetic acid (TCA), trichloroethanol (TCEth), and chloral hydrate (CH) on gap junction mediated intercellular communication in cultured B6C3F1 mouse and F344 rat hepatocytes were assessed. TCE and TCA inhibited intercellular communication in mouse hepatocytes but not in rat hepatocytes. TCEth and CH had no effect on hepatocyte intercellular communication in either rat or mouse cells. TCE and TCA inhibited intercellular communication in both 24-hr-old and freshly plated mouse hepatocytes. Both compounds produced greater inhibition of intercellular communication in freshly plated cells when compared to 24-hr-old cultures. TCE appeared to require cytochrome P450 metabolism by the mouse hepatocytes to exhibit its inhibitory effect on dye coupling since treatment with SKF-525A prevented the inhibition of intercellular communication by TCE. The inhibitory effect of TCA on intercellular communication was unaffected by treatment with SKF-525A. While the species dependent effect of TCE on intercellular communication may be correlated with different rates and extent of metabolism of TCE by rat and mouse hepatocytes, the inhibiting effect of TCA only on mouse hepatocytes suggests that other intrinsic factors in the male mouse make this species more susceptible to the effects of TCE and TCA on gap junction mediated intercellular communication. These findings may account, in part, for the observed species difference in susceptibility to TCE induced liver carcinogenesis.
Klaunig
J E
JE
Department of Pathology, Medical College of Ohio, Toledo 43699.
Ruch
R J
RJ
Lin
E L
EL
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D002697:Chloral Hydrate / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014238:Trichloroacetic Acid / Q000633:toxicity*; D014241:Trichloroethylene / Q000378:metabolism / Q000633:toxicity*
D011725:Pyridines; C013109:metapyrone; D014241:Trichloroethylene; D002697:Chloral Hydrate; D014238:Trichloroacetic Acid