Citation:

Klaunig, J., R. Ruch, AND E. Lin. EFFECTS OF TRICHLOROETHYLENE AND ITS METABOLITES ON RODENT HEPATOCYTE INTERCELLULAR COMMUNICATION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/116 (NTIS PB90107723), 1989.

Description:

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 nongentoxic carcinogens and tumor promoters is the inhibition of gap junction mediated intercellular communication. In the present study, the effects of trichloroethylone (TCE) and its metabolites, trichloracetic acid (TCA), trichloroethanol (TCEth), and chloral hydrate (CH) on gap junction mediatod intercellular communication in cultured B6C3F1 mouse and F344 rat hepatocytes were assessed. TCE and TCA inhibitod intercellular communication in both 24-hr-old and freshly plated mouse hepatocytes. oth compounds produced greater inhibition of intercellular communication in freshly plated cells when compared to 24-hr-old cultures. CE appeared to require cytochrome P450 metabolism by the mouse hepatocytes toexhibit its inhibitory effect on dye coupling since treatment with SKF-525A prevented the inhibition of intercellular communication by TCE. he inhibitory effect of TCA on intercellular communication was unaffected by treatment with SKF-525A. hile 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. hese findigns may account, in part, for the observed species difference in susceptibility to TCE induced liver carcinogenesis.

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