Lawson T A
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Cancer Lett. 1990 Aug;53(1):39-43. doi: 10.1016/0304-3835(90)90008-l.
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.
给完整的和去势的雄性大鼠腹腔注射剂量为20mg/kg的N-亚硝基双(2-氧代丙基)胺(BOP)后,测定其肝脏和鼻黏膜DNA鸟嘌呤O6位的甲基化(O6-MeG)情况。两组大鼠肝脏DNA中O6-MeG的存留情况没有差异。在鼻黏膜中,完整大鼠DNA中检测到的O6-MeG比去势大鼠的多。最大值分别为61(完整大鼠)和35(去势大鼠)nmol/mol鸟嘌呤。半衰期分别为84小时(完整大鼠)和24小时(去势大鼠)。这些情况与O6-MeG-DNA甲基转移酶(MT)活性的变化相对应,去势使鼻黏膜中MT活性增加了6倍,导致鼻黏膜中O6-MeG减少。在肝脏中,去势使MT活性减半,但未使O6-MeG水平产生类似变化。当使用去势大鼠的肝脏匀浆作为活化系统时,BOP在V79细胞中的诱变性增加了近2倍。当使用去势大鼠的鼻黏膜组织匀浆时,诱变性也有类似程度的下降。