Borlak J T, Scott A, Henderson C J, Jenke H J, Wolf C R
University of Reading, Department of Biochemistry and Physiology, UK.
Biochem Pharmacol. 1996 Feb 23;51(4):517-29. doi: 10.1016/0006-2952(95)02228-7.
At the first day of lactation, maternal rats were injected with a single i.p. dose of 100 or 250 mg/kg body weight of a mixture of polychlorinated biphenyls (Aroclor 1254). This treatment caused significant increases in both material and neonatal hepatic cytochrome P-450, cytochrome b5, and cytochrome-c-(P-450) reductase. Transfer of PCBs via lactation resulted in significant increases in hepatic enzyme activities catalysed by neonatal CYP1A1, CYP1A2, CYP2B1, CYP3A1, and CYP2E1 using a variety of substrates. In contrast, the metabolism of dimethylnitrosamine and aminopyrine was only marginally (up to 2-fold) increased in maternal animals four days post treatment. Further measurements showed significant increases in maternal and neonatal epoxide hydrolase, glutathione-S-transferase, and UDP-glucuronyl transferase activities, thus suggesting a coordinated response for an induction of CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1, CYP3A1, and CYP4A1 in both maternal and neonatal CYP2C6, and at the higher dose the expression of neonatal CYP2E1 was significantly reduced. Northern blot analysis provided further evidence for significant increases in maternal and neonatal hepatic CYP1A1, CYP1A2, CYP2B1, and CYP2E1 mRNA, but reduced amounts of CYP2C7 and CYP4A1 mRNA. Additional Northern blot hybridization experiments may suggest an increased expression of the protooncogenes c-Ha-ras and c-raf in the mother and the neonate upon treatment of maternal rats with Aroclor 1254. Lactation itself may result in an increased expression of the latter protooncogenes, but the mRNA of the protooncogenes c-erb A and c-erb B was not detected in any of the tissues examined.
在哺乳期第一天，给母鼠腹腔注射一次剂量为100或250毫克/千克体重的多氯联苯混合物（Aroclor 1254）。这种处理导致母体和新生鼠肝脏中的细胞色素P - 450、细胞色素b5和细胞色素c -（P - 450）还原酶均显著增加。通过乳汁传递的多氯联苯导致新生鼠使用多种底物时，由CYP1A1、CYP1A2、CYP2B1、CYP3A1和CYP2E1催化的肝脏酶活性显著增加。相比之下，在处理后四天，母体动物中二甲亚硝胺和氨基比林的代谢仅略有增加（最多2倍）。进一步测量显示，母体和新生鼠的环氧水解酶、谷胱甘肽 - S -转移酶和尿苷二磷酸葡萄糖醛酸基转移酶活性显著增加，因此表明在母体和新生鼠中，CYP1A1、CYP1A2、CYP2A1、CYP2B1、CYP2E1、CYP3A1和CYP4A1的诱导存在协同反应，并且在较高剂量下，新生鼠CYP2E1的表达显著降低。Northern印迹分析进一步证明母体和新生鼠肝脏中CYP1A1、CYP1A2、CYP2B1和CYP2E1 mRNA显著增加，但CYP2C7和CYP4A1 mRNA量减少。额外的Northern印迹杂交实验可能表明，在用Aroclor 1254处理母鼠后，母体和新生鼠中原癌基因c - Ha - ras和c - raf的表达增加。哺乳本身可能导致后一种原癌基因的表达增加，但在所检查的任何组织中均未检测到原癌基因c - erb A和c - erb B的mRNA。
