Singletary K W, Milner J A
J Natl Cancer Inst. 1987 Apr;78(4):727-33.
Hepatocytes were isolated from noninbred Sprague-Dawley rats previously fed diets containing 7.5 or 15% protein. These hepatocytes were incubated in the presence of exogenous DNA for examination of their ability to metabolize 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] and release reactive DNA-binding metabolites to the medium. An increased formation of extracellular water-soluble metabolites of DMBA was observed in hepatocyte cultures from rats fed a 15% protein diet compared with that in cells from rats fed 7.5% protein. As dietary protein increased, there was a reduction in the release of DNA-binding metabolites by isolated hepatocytes. Bay-region dihydrodiol-epoxide adducts were formed with extracellular calf thymus DNA and hepatic DNA. However, most of the binding of DMBA with extracellular and intracellular DNA was due to unidentified DMBA-DNA adducts that eluted, upon reversed-phase chromatography, after the bay-region dihydrodiol-epoxide DMBA adducts were formed. The present studies show that feeding animals diets that are limiting in protein results in a decrease in DMBA detoxification and an increase in excretion of reactive DMBA metabolites from the liver. These results may explain the previously observed influence of dietary protein on the initiation of DMBA-induced mammary carcinogenesis in the rat.
从先前喂食含7.5%或15%蛋白质饮食的非近交系Sprague-Dawley大鼠中分离出肝细胞。将这些肝细胞在外源DNA存在的情况下进行培养，以检测它们代谢7,12-二甲基苯并[a]蒽[（DMBA），化学物质登录号：57-97-6]并向培养基中释放具有反应活性的DNA结合代谢物的能力。与喂食7.5%蛋白质饮食的大鼠的肝细胞培养物相比，在喂食15%蛋白质饮食的大鼠的肝细胞培养物中观察到DMBA的细胞外水溶性代谢物形成增加。随着饮食中蛋白质含量的增加，分离出的肝细胞释放的DNA结合代谢物减少。湾区二氢二醇环氧化物加合物与细胞外小牛胸腺DNA和肝DNA形成。然而，DMBA与细胞外和细胞内DNA的大部分结合是由于未鉴定的DMBA-DNA加合物，在反相色谱分析中，这些加合物在湾区二氢二醇环氧化物DMBA加合物形成后被洗脱。目前的研究表明，给动物喂食蛋白质含量受限的饮食会导致DMBA解毒作用降低，肝脏中具有反应活性的DMBA代谢物排泄增加。这些结果可能解释了先前观察到的饮食蛋白质对大鼠DMBA诱导的乳腺癌发生起始阶段的影响。
