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) μmol/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.