CHEMICAL MODIFICATION OF VIRAL RIBONUCLEIC ACID .8. CHEMICAL AND BIOLOGICAL EFFECTS OF METHYLATING AGENTS AND NITROSOGUANIDINE ON TOBACCO MOSAIC VIRUS

The ribonucleic acid in the tobacco mosaic virus particle reacts very sluggishly with nitrosoguanidine, as compared with dimethyl sulfate, and with the free ribonucleic acid reacting with either reagent. Yet, the nitrosoguanidine tobacco mosaic virus reaction is the only one of these reactions which is highly mutagenic. The distribution of the few methyl groups that could be introduced into the intraviral ribonucleic acid (two per mole, 2 X 106 daltons, during 5 days at 37°) was unusual in that the extent of methylation of cytosine approached that of guanine, and that the 1-methylation of adenine was somewhat depressed. In contrast, dimethyl sulfate caused (in 24 hr at 0°) about 97 guanine methylations and a total of 3 other methylations at a similar level of inactivation (2-3 inactivating events), associated with little mutagenesis. Deamination of adenine was found not to account for the high mutagenic action of nitrosoguanidine on tobacco mosaic virus but the possibility that mutagenesis is a consequence of cytosine deaminations has not been excluded. Alternatively, the mutagenicity of this reaction may be due to the increased methylation of cytosine. © 1969, American Chemical Society. All rights reserved.