Abstract
The hepatotoxic compound bromobenzene binds to DNA, RNA, and proteins of rat and mouse liver in vivo. Binding to a significant extent is also detected in mouse kidney. The covalent binding index (CBI) of bromobenzene is comparable to CBI values of moderately oncogenic substances. The enzyme-mediated in vitro interaction of bromobenzene with calf thyumus DNA and synthetic polyribonucleotides is effected only by microsomes, especially those from mouse and rat liver. Microsomes from mouse lung are also efficient in bioactivating bromobenzene to interact with DNA. Among polyribonucleotides, poly(G) and poly(A) are the most labeled substrates. The suppression of binding to DNA by SKF 525-A and the induction of microsomal activity by a pretreatment with phenobarbitone in vivo confirm that bromobenzene is bioactivated by a P-450 dependent-microsomal mixed function oxidase system. The covalent binding can be the main event to determine the possible carcinogenicity by genotoxic mechanisms. Bromobenzene is photoactivated by ultraviolet light (lambda = 254 nm) to forms capable of interacting with DNA in vitro; the binding is linear up to time.
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