Activation of N-nitrosobis(2-oxopropyl)amine by liver and nasal mucosa tissue from intact and castrated male rats.
Methylation of liver and nasal mucosal DNA at the O6 position of guanine (O6-MeG) was measured in intact and castrated male rats after a dose of N-nitrosobis(2-oxopropyl)amine (BOP) (20 mg/kg; i.p.). There were no differences in O6-MeG persistence in liver DNA from either group. In the nasal mucosa more O6-MeG was detected in DNA from intact rats than in that from castrated rats. The maximum values were 61 (intact) and 35 (castrated) mumols/mol guanine. T/2 were 84 h (intact) and 24 h (castrated). These situations corresponded with changes in O6-MeG-DNAmethyl-transferase (MT) activity, which increased 6-fold in the nasal mucosa by castration resulting in less O6-MeG in the nasal mucosa. In the liver castration halved MT activity but did not produce a comparable change in O6-MeG levels. The mutagenicity of BOP in V79 cells increased almost 2-fold when a liver homogenate from castrated rats was used as the activating system. There was a comparable decline in mutagenicity when a nasal mucosa tissue homogenate from castrated rats was used.
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
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Lawson
D000818:Animals; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity; D009154:Mutation; D009297:Nasal Mucosa / Q000201:enzymology / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism* / Q000633:toxicity; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains
D009153:Mutagens; D009602:Nitrosamines; D006147:Guanine; C013622:nitrosobis(2-oxopropyl)amine; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase