DNA alkylation and neuro-oncogenesis by 3,3-dimethyl-1-phenyltriazene

Abstract

The role of DNA alkylation by the neurooncogenic agent 3,3-dimethyl-1-phenyltriazene (DMPT) was investigated perinatally and in adult rats. Following a single subcutaneous injection of¹⁴C-DMPT (100 mg/kg) on the 21st day of gestation, the concentration of methylated purines was similar in both fetal liver and brain whereas during postnatal growth this treatment resulted in an increasingly preferential methylation of liver DNA. In 30-day-old and adult rats the concentration of 7-methylguanine in liver was about 8 times higher in brain DNA, suggesting that during prenatal development both liver and brain DNA are transplacentally methylated by a proximate carcinogen produced by maternal organs. Multiple doses of¹⁴C-DMPT (50 mg/kg) to adult rats led to a preferential accumulation of O⁶-methylguanine in cerebral DNA. This supports the hypothesis that the deficient repair excision capacity of the central nervous system is a significant factor in the organ-specific carcinogenicity of DMPT and related carcinogens.