Methylation in vivo of Guanine in the Nucleic Acids of Rat Testes by Methyl Methane Sulphonate

Abstract

TREATMENT of male rats with a single intraperitoneal dose of 50 or 100 mg/kg body weight of methyl methane sulphonate results in infertility during the second and third week after the injection¹. This infertility is caused not by aspermia but by a dominant lethal mutation in the sperm which are selectively affected at the late spermatid or early spermatozoa stage. The mutation does not interfere with the fertilization of the ova but the resulting embryos die in utero². It has been assumed that this biological action of methyl methane sulphonate is connected with its properties as an alkylating agent. When a bacteriophage is inactivated by treatment with methyl methane sulphonate, guanine and adenine of the bacteriophage DNA are methylated to 7-methyl guanine, 3-methyl adenine, and 1-methyl adenine in proportion 78 : 20 : 2 (ref. 3). We have now found that an intravenous injection of methyl methane sulphonate methylates the 7 position of the guanine of DNA and RNA in rat testes.