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.
Bochert
G
G
Institut für Toxikologie und Embryopharmakologie, FU Berlin, Germany.
Platzek
T
T
Rahm
U
U
Neubert
D
D
D000014:Abnormalities, Drug-Induced; D000478:Alkylation; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D008770:Methylnitrosourea / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011247:Pregnancy
D006147:Guanine; D008770:Methylnitrosourea; D004247:DNA; C008449:O-(6)-methylguanine