Dutta-Choudhury T A, Bak B H, Guzman R C
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Carcinogenesis. 1991 Oct;12(10):1795-800. doi: 10.1093/carcin/12.10.1795.
O6-Methylguanine-DNA methyltransferase (O6-MT) is a DNA repair protein that reverses alkylation damage at the O6 position of guanine. In the process, O6-MT undergoes suicide inactivation. To determine if this enzyme might be regulated by pregnancy-associated hormones we measured changes in the level of O6-MT in isolated mouse mammary epithelial cell homogenates during different reproductive states. These were pregnancy, ectopic pituitary transplantation, proestrus/estrus and diestrus. O6-MT levels were found to be similar in mice in proestrus/estrus (0.95 fmol/micrograms DNA) as compared to diestrus (0.94 fmol/micrograms DNA) and also mixed populations of virgin mice (1.09 fmol/micrograms DNA). A mean for all virgin mice (0.97 fmol/micrograms DNA) was used as a comparative index. O6-MT decreased 2-fold during pregnancy in mammary epithelial cells to a mean value of 0.45 fmol/micrograms DNA (P less than 0.05). A smaller decrease (0.65 fmol/micrograms DNA; P less than 0.01) in mammary epithelial cells was found at 3 weeks following pituitary isograft. The repair capacity of mammary epithelial cells to liver was compared by measurements made in liver homogenates from the same mice and are approximately 3-fold higher in liver from virgin mice (3.2 fmol/micrograms DNA) than mammary gland. Liver levels of O6-MT increased in pregnant (5.3 fmol/micrograms DNA) and pituitary transplanted (3.9 fmol/micrograms DNA) mice, and were 5- and 4-fold higher than the concentration in virgin mammary epithelial cells respectively.
O6-甲基鸟嘌呤-DNA甲基转移酶（O6-MT）是一种DNA修复蛋白，可逆转鸟嘌呤O6位的烷基化损伤。在此过程中，O6-MT会发生自杀性失活。为了确定这种酶是否受妊娠相关激素的调节，我们测量了处于不同生殖状态的分离小鼠乳腺上皮细胞匀浆中O6-MT水平的变化。这些状态包括妊娠、异位垂体移植、动情前期/发情期和动情后期。发现动情前期/发情期小鼠（0.95飞摩尔/微克DNA）的O6-MT水平与动情后期（0.94飞摩尔/微克DNA）以及未交配的混合小鼠群体（1.09飞摩尔/微克DNA）相似。所有未交配小鼠的平均值（0.97飞摩尔/微克DNA）用作比较指标。妊娠期间乳腺上皮细胞中的O6-MT降低了2倍，平均值为0.45飞摩尔/微克DNA（P<0.05）。垂体同种移植后3周，乳腺上皮细胞中出现较小程度的降低（0.65飞摩尔/微克DNA；P<0.01）。通过对同一小鼠肝脏匀浆的测量比较了乳腺上皮细胞与肝脏的修复能力，未交配小鼠肝脏中的修复能力（3.2飞摩尔/微克DNA）比乳腺大约高3倍。妊娠小鼠（5.3飞摩尔/微克DNA）和垂体移植小鼠（3.9飞摩尔/微克DNA）肝脏中的O6-MT水平升高，分别比未交配乳腺上皮细胞中的浓度高5倍和4倍。
