Metabolic activation of carbon tetrachloride by the cervico-vaginal epithelium in rodents.
The metabolism and binding of 14C-labelled carbon tetrachloride (CCl4) in the genital tract of female adult or juvenile NMRI-mice and Sprague-Dawley rats (mainly in the pro-oestrous/oestrous stage) and an adult New Zealand rabbit were studied. A marked irreversible binding of radioactivity in the squamous cervico-vaginal epithelium of mice given intravenous injections of 14C-CCl4 was revealed by autoradiography of solvent-extracted tissue. The localization of binding in the mouse genital tract incubated with 14C-CCl4 under air was similar to that observed in vivo. Bound radioactivity was also present in the cylindrical epithelium of the rabbit vagina incubated with 14C-CCl4 in vitro. For a comparison, no preferential binding of radiolabelled diethylstilbestrol or ethinylestradiol was observed in the mouse cervico-vaginal epithelium. The level of irreversible binding to PMSG-primed (pregnant mare's serum gonadotrophin) vaginal epithelial 100 x g supernatants of mice and rats incubated with 14C-CCl4 under air was low. Addition of the reducing agent dithionite to the incubations increased the binding in the vaginal epithelium 20-fold. In juvenile mice and rats injected with 14C-CCl4, the levels of metabolites in the epithelium were low, whereas PMSG-primed juvenile rats contained a higher level of metabolites. The results show that the cervico-vaginal epithelium can metabolically activate CCl4 to reactive metabolites and suggest that the metabolism is under endocrine control.
Brittebo
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EB
Department of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala Biomedical Center.
Brandt
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I
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002245:Carbon Dioxide / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000493:pharmacokinetics*; D002584:Cervix Uteri / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014621:Vagina / Q000378:metabolism*
D002245:Carbon Dioxide; D004997:Ethinyl Estradiol; D004054:Diethylstilbestrol; D002251:Carbon Tetrachloride