The interactive hepatotoxicity of CCI4 and chlordecone, at an individually nontoxic dosage, was studied in neonatal and young developing rats. The well-documented amplification of CCI4 (100 μL/kg) hepatotoxicity and lethality by prior dietary exposure to chlordecone (10 ppm, for 15 d) was absent in neonatal and developing rats through 35 d of age. The chlordecone-potentiated hepatotoxicity and lethality of CCI4 was partially expressed in 45-d-old rats and fully expressed in 60-d-old rats. Although hepatic microsomal cytochrome P-450 content in 2? or 5-d-old rats was significantly lower than that in older age groups, the cytochrome P-450 content was not significantly different between 35-, 45-, and 60-d-old chlordeconetreated rats. During postnatal development, the ongoing hepatocellular proliferation declined in a biphasic manner, more rapidly up to 20 d and slowly thereafter, as indicated by 3H-thymidine incorporation in hepatic nuclear DNA. This pattern of postnatal liver proliferation and growth was not altered by exposure to chlordecone. In vivo metabolism of CCI4, in terms of 14CO2 production derived from 14CCI4 and 14CCI4 metabolites bound to hepatic tissue, was not significantly different between 35-, 45-, and 60-d-old chlordecone-treated rats, whereas CCI4-stimulated hepatocellular regeneration in 35-d-old chlordecone-treated rats was significantly higher than in 45? or 60-d-old chlordecone-treated rats, as indicated by 3H-thymidine incorporation into hepatic DNA and histomorphometric analysis. These data suggest that the absence of potentiation of CCI4 toxicity by chlordecone in postnatally developing rats is well correlated with the presence of ongoing and stimulatable hepatocellular regenerative activity.
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