Reactions of vinyl chloride with RNA and DNA of various mouse tissues in vivo.

Abstract

The irreversible binding of 14C-vinyl chloride metabolites to RNA and DNA of mouse brain, lung, liver, kidney, spleen, pancreas, and testes after a single i.p. injection has been studied. Hydrolysates of nucleic acids from selected organs were separated on Aminex A6 for quantitation of alkylation products. Radioactivity in nucleic acids was registered in all of the studied organs with the exception of brain. RNA from spleen, pancreas and liver, and DNA from spleen and liver contained the highest amounts of radioactivity. In nucleic acids from spleen and pancreas, both organs of high metabolic activity, the entire radioactivity was found metabolically incorporated as C1-fragments. In RNA of kidney and liver, a large part of the radioactivity was also present as incorporated C1-fragments, but 3,N4-ethenocytidine (in kidney) as well as 1,N6-ethenoadenosine and 1,N6-ethenoadenine (in kidney and liver) were identified as alkylation products. In liver DNA, incorporation of C1-fragments was insignificant, indicating different interactions of vinyl chloride metabolites (C1-fragments and alkylating products) with RNA and DNA. The elution profiles of radioactivity in hydrolysates of liver DNA were dominated by an alkylation product of unknown structure (probably a derivative of deoxyguanosine). Possibly, 1,N6-ethenodeoxyadenosine and 1,N6-ethenoadenine were also present in liver DNA. The results are consistent with the ability of vinyl chloride to act as a multipotent carcinogen by alkylation of DNA in several tissues.