Comparison of 7,12-dimethylbenz[a]anthracene metabolism and DNA binding in mammary epithelial cells from three rat strains with differing susceptibilities to mammary carcinogenesis.
Comparison of 7,12-dimethylbenz[a]anthracene metabolism and DNA binding in mammary epithelial cells from three rat strains with differing susceptibilities to mammary carcinogenesis.
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比较具有不同乳腺癌易感性的三种大鼠品系的乳腺上皮细胞中 7,12-二甲基苯并[a]蒽的代谢和 DNA 结合。
DOI：
10.1093/carcin/9.11.2099
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发表时间：
1988
期刊：
影响因子：
4.7
通讯作者：
Gould,MN
中科院分区：
文献类型：
--
作者：
Moore,CJ;Tricomi,WA;Gould,MN
本文研究了多环芳烃如7，12-二甲基苯并[a]蒽（DMBA）诱发三种大鼠乳腺癌的能力。Wistar/Furth（WF）大鼠对DMBA诱导的乳腺癌发生高度敏感，Copenhagen（Cop）大鼠完全抵抗，Fischer 344（F344）大鼠具有中等敏感性。我们以前已经表明，WF大鼠具有“增强子基因”，这增强了诱发乳腺癌的易感性。然而，耐药鼠拥有一个单一的“抑制”基因，可以完全抵抗乳腺癌。这两种基因类型在F344大鼠中明显缺失。为了确定这些增强子和抑制基因可能的作用机制，我们研究了DMBA代谢和DNA结合在乳腺上皮细胞分离的每个大鼠品系。代谢和DNA结合的定量分析表明菌株之间没有显着差异。此外，DMBA代谢物和DMBA-DNA加合物的HPLC分析基本相同。这些数据表明，这些大鼠品系中控制乳腺癌易感性和抗性的基因可能在致癌过程的后期阶段是活跃的。
The capacity of polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz[a]anthracene (DMBA) to induce mammary carcinomas has been studied in three rat strains. Wistar/Furth (WF) rats are highly susceptible to DMBA-induced mammary carcinogenesis, Copenhagen (Cop) rats are completely resistant, and Fischer 344 (F344) rats have an intermediate susceptibility. We have previously shown that WF rats possess ‘enhancer genes’, which enhance susceptibility to induced mammary cancer. Cop rats, however, possess a single ‘suppressor’ gene which confers complete resistance to mammary cancer. Both gene types are apparently absent in F344 rats. In order to determine possible mechanisms of action of these enhancer and suppressor genes, we have examined DMBA metabolism and DNA binding in mammary epithelial cells isolated from each rat strain. Quantitative analyses of both metabolism and DNA binding indicate no significant differences among the strains. In addition, HPLC analyses of DMBA metabolites and DMBA-DNA adducts were essentially identical. These data suggest that the genes controlling susceptibility and resistance to mammary carcinogenesis in these rat strains are likely to be active at later stages of the carcinogenic process.