Microsome-mediated alkylation of rat liver initiator tRNA by 3,3-dimethyl-l-phenyltriazene and its ring-chlorinated derivatives

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Abstract
3,3-[3H]Dimethyl-1-phenyltriazene, 1-(4-chlorophenyl)-3,3-[3H]dimethyltriazene and 3,3-[3H]dimethyl-1-(2,4,6-trichlorophenyl)triazine methylate initiator tRNA in vitro only after pre-incubation with microsomal enzymes and NADPH. The finding confirms that procarcinogenic dialkyl aryltriazenes must be enzymatically converted into reactive metabolites, presumably into the corresponding monoalkyltriazenes, which ultimately react with tRNA. The methylation at 37.degree. C requires 40-60 min and individual triazenes showed differential alkylating capacity if tRNA was the limiting factor. Enzymatic hydrolysis of the modified initiator tRNA, followed by separation of nucleosides on Sephadex G10 or Dowex 50 columns, revealed that 7-methylguanosine was the principal labeled product. The methylated tRNA showed a significantly increased acceptance for L-methionine. It appears that methylation of initiator tRNA at N7 of guanine affected the conformation of initiator tRNA and rendered the nucleic acid more accessible for cognate aminoacyl-tRNA synthetase.