The reaction of mustard gas with nucleic acids in vitro and in vivo

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Abstract
A study was made of the reaction of S35-labeled mustard gas with nucleic acid in neutral aqueous solution at 37[degree] with a low concentration of mustard gas. The only detectable reaction with both ribonucleic acid and deoxyribonucleic acid was at N-7 of guanine moieties, the hydrolysis products having chromatographic properties identical with those obtained from guanosine and mustard gas. The principal product from nucleic acid and mustard gas, 7-([beta]-hydroxyethylthioethyl)guanine, was synthesized. Ribonucleic acid alkylated by mustard gas is stable in neutral aqueous solution but alkylated deoxyribonucleic acid decomposes with loss of 7-alkylguanine. Tobacco mosaic virus, Bacillus megaterium and cells of the Ehrlich ascites tumor were treated with S35-labelled mustard gas; the extent of reaction with nucleic acid was about the same as that with protein. The site of reaction with nucleic acid was shown, as in the case of pure nucleic acid, to be at N-7 of guanine moieties. Mice bearing the Ehrlich ascites tumor were injected with S35-labelled mustard gas and the nucleic acid or the tumor cells were shown to react in the same way as in vitro. Previous work on the reactions of alkylating agents with nucleic acids is discussed in relation to the present findings.