In vivo and in vitro covalent binding of chlorobenzene to nucleic acids.
At 22 hr after ip injection into male Wistar rats and BALB/c mice, chlorobenzene was covalently bound to DNA, RNA and proteins of the liver, kidney and lung, as has been found with various weak carcinogens. A microsome-mediated interaction with DNA occurred in vitro. The interaction was enhanced by pretreatment in vivo with phenobarbitone but was suppressed by addition of 2-diethylaminoethyl-2,2-diphenylvalerate HC1 in vitro. These results indicate the involvement of cytochrome P-450. Liver microsomes were efficient bioactivators, whereas cytosol was ineffective. The extent of in vitro interaction of chlorobenzene with synthetic polyribonucleotides was of the same order as that with DNA. Finally, ultraviolet irradiation (lambda = 254 nm or lambda max = 365 nm) activated this environmental contaminant to forms capable of interacting with DNA. The results represent evidence for genotoxicity of chlorobenzene.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002722:Chlorobenzenes / Q000378:metabolism* / Q000633:toxicity; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D010777:Photochemistry; D011485:Protein Binding; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D002722:Chlorobenzenes; D009696:Nucleic Acids; C031294:chlorobenzene; D010634:Phenobarbital