In vivo replication of hepatic deoxyribonucleic acid of rats treated with dimethylnitrosamine: presence of dimethylnitrosamine-induced O6-methylguanine, N7-methylguanine, and N3-methyladenine in the replicated hybrid deoxyribonucleic acid.
Experiments were designed to determine whether some chemical lesions such as O6-methylguanine, N7-methylguanine, and N3-methyladenine induced in rat liver DNA by the hepatocarcinogen dimethylnitrosamine permit replication in vivo. For this purpose, [14C]dimethylnitrosamine was administered to methylate the parental strand of liver DNA. Four hours later, a time period when the carcinogen cannot be detected in either the liver or the blood, rats were subjected to partial hepatectomy in order to induce DNA replication. During the S phase, 5-bromo-2-deoxyuridine was administered to render the newly made strands heavy. The rebanded, hybrid, hepatic DNA of density 1.714 g/cm3 and greater was pooled from the neutral cesium chloride gradient, dialyzed, and lyophilized. The hybrid DNA was then treated with S1 nuclease to digest any single-stranded regions. The results obtained indicated the presence of O6-methylguanine, N7-methylguanine, and N3-methyladenine in S1 nuclease resistant, hybrid DNA. The results are interpreted to indicate that these chemical lesions permitted in vivo DNA replication.
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D004261:DNA Replication / Q000187:drug effects*; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009693:Nucleic Acid Hybridization; D051381:Rats
C025946:3-methyladenine; D006147:Guanine; C008450:7-methylguanine; C008449:O-(6)-methylguanine; D000225:Adenine; D004128:Dimethylnitrosamine