O6-methylguanine accumulates in DNA of mammary glands after administration of N-methyl-N-nitrosourea to rats.
N-Methyl-N-nitrosourea (MNU) induces mammary carcinoma in female rats when given intravenously. After a single intravenous dose of N-methyl-N-nitrosourea (5 mg/100 g body wt.), we were unable to detect a shift of rat mammary gland DNA on an alkaline sucrose gradient. However, the alkylated products in DNA, 7-methylguanine and O6-methylguanine, were determined at various times following treatment with N-methyl-N-nitrosourea. O6-Methylguanine was removed from the DNA at a slower rate than 7-methylguanine and increased in the DNA with a second injection of N-methyl-N-nitrosourea. 3-Methyladenine was not detected in DNA from the mammary gland of the rat. These data support previous work with brain and bladder that suggest the persistence of O6-methylguanine in DNA might be involved in the induction of cancer by N-methyl-N-nitrosourea.
D000818:Animals; D001921:Brain / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced; D008745:Methylation; D008770:Methylnitrosourea / Q000633:toxicity*; D009607:Nitrosourea Compounds / Q000633:toxicity*; D051381:Rats; D001743:Urinary Bladder / Q000187:drug effects
D009607:Nitrosourea Compounds; D006147:Guanine; D008770:Methylnitrosourea; D004247:DNA; C008449:O-(6)-methylguanine