Species differences in the interaction between CCI4 reactive metabolites and liver DNA or nuclear protein fractions

Publisher Website
Google Scholar
Abstract
CCI4 has been reported to be a liver carcinogen for several mice strains, for Syrian Golden hamsters, but not for Sprague-Dawley rats. CCI4 is an experimental carcinogen for which no convincing evidence of mutagenicity is available despite the fact that CCI4 reactive metabolites bind covalently to liver DNA. Here we describe studies on the relationship between the intensities of the covalent binding (CB) of CCI4 reactive metabolites to liver DNA and nuclear proteins either in vivo or in vitro after activation to reactive metabolites by nuclear preparations, considering the known susceptibility of the C3H mice, Syrian Golden hamsters and Sprague-Dawley rats to CCI4. There was no correlation between the intensity of CCI4 carcinogenic effects on the liver and CB of CCI4 reactive metabolites to total DNA either in vitro or in vivo. A good correlation between carcinogenicity and CB to total nuclear proteins (in vivo or in vitro was found. Nuclear protein fractionation studies revealed CB of CCI4 reactive metabolites to both histone and non-histone proteins when nuclear preparations activated CCI4 either in the presence or absence of NADPH. Acidic and residual nuclear proteins were the favorite targets of the interaction with CCI4 reactive metabolites. A good correlation between CB to these nuclear protein fractions and CCI4 carcinogenicity in the three species was found.