Alkylation of RNA by Vinyl Chloride and Vinyl Bromide Metabolites in Vivo: Effect on Protein Biosynthesis

Abstract

Alkylation of DNA is viewed as representing the initial critical step in carcinogenesis induced by chemical substances. Vinyl chloride and vinyl bromide, compounds with proven carcinogenic potency toward the liver, are biotransformed to reactive metabolites which covalently bind to DNA (see Bolt et al. 1980). Furthermore, extensive covalent binding of metabolites of both vinyl chloride (Laib and Bolt 1977, 1978) and vinyl bromide (Ottenwälder et al. 1979) occurs to RNA of liver when rats are exposed to both vinyl halides. Defined products of alkylation are 1,N⁶-ethenoadenosine (Laib and Bolt 1777; Ottenwälder et al. 1979) and 3,N⁴-ethenocytidine (Laib and Bolt 1978; Ottenwälder et al. 1979). This type of alkylation is also observed in experiments in vitro after using different methodological approaches (Laib and Bolt 1980). Hence, the question arises as to possible biological consequences of an alkylation of RNA by metabolites of vinyl chloride and vinyl bromide. Experiments were designed to study the influence of such an RNA alkylation on protein biosynthesis, using a defined wheat-germ translation system in vitro.