Abstract
14 C from 14 CCl 4 irreversibly binds in vivo to liver DNA from strain A J mice and Sprague-Dawley rats. Binding of 14 CCl 4 to DNA was also observed in vitro in incubation mixtures containing microsomes and a NADPH-generating system as well as in tissue slices. Chemically induced ·CCl 3 (CCl 4 + benzoyl peroxide system) intensively binds to DNA. Liver nuclear proteins also irreversibly bind CCl 4 metabolites. Nuclear protein fractionation studies revealed that deoxyribonucleoproteins, acidic proteins, histones, and residual proteins are the favorite targets of metabolite interaction. Nuclear sap proteins are less intensively labeled. Nuclear lipids were markedly labeled by CCl 4 reactive metabolites. Most of the label is in the phospholipid fraction and diphosphatidylglycerol is most intensively labeled; phosphatidylethanolamine, phosphatidylcholine, lysophosphatidylcholine, and sphingomyeline are also labeled by metabolites. The interaction of ·CCl 3 with DNA and nuclear proteins could be relevant to CCl 4-induced liver tumors and hepatotoxic effects.
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