Vainio H
Arch Environ Contam Toxicol. 1976;4(2):201-16. doi: 10.1007/BF02221024.
DDT was administered to the guinea pig, mouse and rat either ig or ip and to the hamster ig in order to investigate variations in the response of hepatic and duodenal drug-metabolizing enzymes to DDT. The intragastric dose (160 mg/kg) was found to produce gastric bleeding and severe tremor in rats and mice but not in other rodents. The hepatic aryl hydrocarbon hydroxylase activity and cytochrome P-450 concentration decreased after the ig administration of DDT to rats, mice and guinea pigs but in hamsters the activiy of aryl hydrocarbon hydroxylase and cytochrome P-450 concentration increased 12 hr after the dosage. The aryl hydrocarbon hydroxylase activity decreased also in the duodenal mucosa of the rat after the ig administration of DDT. The ip dose had no effects on the hepatic or duodenal monooxygenase system in 12 hr. The UDPglucuronosyltransferase activity was slightly lowered in hepatic microsomes of the rat and mouse after the ig dose of DDT, but the decrease was more profound when measured after in vitro trypsin digestion of microsomes. The trypsin digestion activated the hepatic UDPglucuronosyltransferase in all the species studied, i.e., guinea pig, hamster, mouse and rat (3-, 3-, 5-, and 8-fold, respectively). The duodenal UDPglucuronosyltransferase activity was not affected by DDT administration in any of the species studied. The results suggest that the acute toxic effects of DDT are species-dependent and the administration route is important in DDT toxicity. The hydroxylation step in drug metabolism is more sensitive to DDT than the glucuronidation step.
为了研究肝和十二指肠药物代谢酶对滴滴涕（DDT）反应的差异，分别经口（ig）或腹腔注射（ip）给予豚鼠、小鼠和大鼠DDT，并经口给予仓鼠DDT。发现经口剂量（160mg/kg）可使大鼠和小鼠出现胃出血和严重震颤，但其他啮齿动物未出现。经口给予大鼠、小鼠和豚鼠DDT后，其肝芳烃羟化酶活性和细胞色素P-450浓度降低，但仓鼠在给药12小时后，芳烃羟化酶活性和细胞色素P-450浓度增加。经口给予DDT后，大鼠十二指肠黏膜中的芳烃羟化酶活性也降低。腹腔注射剂量在12小时内对肝或十二指肠单加氧酶系统无影响。经口给予DDT后，大鼠和小鼠肝微粒体中的尿苷二磷酸葡萄糖醛酸基转移酶活性略有降低，但在微粒体经体外胰蛋白酶消化后测量时，降低更为显著。胰蛋白酶消化激活了所研究的所有物种（即豚鼠、仓鼠、小鼠和大鼠，分别为3倍、3倍、5倍和8倍）的肝尿苷二磷酸葡萄糖醛酸基转移酶。在所研究的任何物种中，十二指肠尿苷二磷酸葡萄糖醛酸基转移酶活性均不受DDT给药的影响。结果表明，DDT的急性毒性作用具有物种依赖性，给药途径对DDT毒性很重要。药物代谢中的羟化步骤比葡萄糖醛酸化步骤对DDT更敏感。
