Embryotoxicity induced by alkylating agents: 6. DNA adduct formation induced by methylnitrosourea in mouse embryos.

Formation of DNA adducts in 11-day-old mouse embryos was studied by measuring the initial alkylation rates of the methylated purine bases 7-methylguanine, O6-methylguanine, and 3-methyladenine. In the first part of the studies the adduct rates were measured in the teratogenic dose range (ED10-ED90, 2.7-5.6 mg/kg). These results were compared with similar data obtained from studies with ethylmethanesulfonate and acetoxymethyl-methylnitrosamine. For the three investigated substances a correlation was found between the initial adduct rate of O6-alkylguanine in the DNA of the embryos and the teratogenic potency. In the second part of the study the rate of adduct formation was measured in the sub-teratogenic dose range. These data will be used for molecular dosimetry in a risk assessment of low doses.