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ALKYLATION OF RAT BRAIN NUCLEIC ACIDS BY N‐METHYL‐N‐NITROSOUREA AND METHYL METHANESULPHONATE

Abstract— Alkylation of rat brain nucleic acids in vivo was measured after a single intravenous injection (1 mmol/kg body wt.) of N‐[14C]methyl‐N‐nitrosourea and [14C]methyl methanesulphonate. The main product with both compounds was 7‐methylguanine, The extents of methylation on this position in DNA and RNA were similar with methylnitrosourea but methyl methanesulphonate produced twice as much 7‐methylguanine in DNA as in cytoplasmic RNA. Brain DNA from rats treated with labelled methylnitrosourea contained radioactive O6‐methylguanine, accounting for about 12 per cent of the radioactivity present as 7‐methylguanine and cytoplasmic RNA contained about half this amount of O6‐methylguanine. Neither DNA nor cytoplasmic RNA from methyl methanesulphonatetreated rats contained any detectable O6‐methylguanine. Treatment with both compounds resulted in varying small amounts of methylation of other nucleic acid bases including 1‐methyladenine, 3‐methyladenine and 3‐methylcytosine. The possible relevance of alkylation of brain nucleic acids to the induction of brain tumours is discussed.