Chang B D, Beattie C W, Hussain R A, Anderson C H
Specialized Cancer Center, University of Illinois at Chicago 60612.
Cancer Lett. 1993 Nov 30;75(1):11-8. doi: 10.1016/0304-3835(93)90201-j.
N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor incidence and tumor number per rat, is directly correlated with an increase in the circulating level of estrogen(s) at the time of carcinogen administration and subsequent mammary epithelial O6-methylguanine content. We report that, expression of O6-alkyltransferase (AGT) is also regulated by reproductive hormones in a tissue specific manner. The level of mammary epithelial cell AGT activity on estrus (0.47 pmol/mg protein) and proestrus (0.32) was significantly higher than on metestrus (0.14) (P < 0.05, estrus vs. metestrus). However, no change was observed in liver AGT activity (0.52 pmol/mg protein). In contrast, the mean level of AGT protein was not significantly different between tumors from rats injected with MNU on different days of the estrous cycle. In conclusion, the different tumor biologies resulting from carcinogen injection on different days of the estrous cycle may be partially explained by variation in levels of DNA repair activity. However, the cells in the resulting tumors did not continue an obligatory differential expression of the AGT activity consistent with their stage of initiation.
N-甲基-N-亚硝基脲（MNU）诱导的大鼠乳腺肿瘤发生率及每只大鼠的肿瘤数量，与给予致癌物时循环雌激素水平的升高以及随后乳腺上皮细胞的O6-甲基鸟嘌呤含量直接相关。我们报告，O6-烷基转移酶（AGT）的表达也受生殖激素以组织特异性方式调节。发情期（0.47 pmol/mg蛋白质）和动情前期（0.32）时乳腺上皮细胞AGT活性水平显著高于间情期（0.14）（P < 0.05，发情期与间情期相比）。然而，肝脏AGT活性（0.52 pmol/mg蛋白质）未观察到变化。相反，在发情周期不同日子注射MNU的大鼠所形成肿瘤之间，AGT蛋白的平均水平无显著差异。总之，发情周期不同日子注射致癌物导致的不同肿瘤生物学特性，可能部分由DNA修复活性水平的变化来解释。然而，所形成肿瘤中的细胞并未继续与其起始阶段一致的AGT活性的强制性差异表达。
