Lubet R A, Guengerich F P, Nims R W
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701.
Arch Environ Contam Toxicol. 1990 Mar-Apr;19(2):157-63. doi: 10.1007/BF01056082.
Methods of biochemical monitoring of individual animals for exposure to environmental contaminants are of great potential use. The hepatic metabolism of various alkoxyresorufins, which are highly specific substrates for certain forms of cytochrome(s) P450, is highly induced by a variety of environmental contaminants. Thus, the O-dealkylation of pentoxy- or benzyloxyresorufin was induced greater than 20-fold in the rat by alpha-hexachlorocyclohexane, 2,4,5,2',4',5'-hexabromobiphenyl, DDT and Aroclor-1254, while the metabolism of ethoxyresorufin was highly induced by 5,6-benzoflavone, 3,4,5,3',4',5'-hexabromobiphenyl and Aroclor-1254. Additionally, rats exposed to diets containing as little as 12 ppm DDT displayed greater than five-fold increases in the rate of hepatic O-dealkylation of benzyloxyresorufin. Induction of the hepatic metabolism of these resorufin ethers in 9000 xg supernatant fractions taken from rats exposed to potential environmental contaminants may constitute a valuable diagnostic indicator of the presence of a variety of pollutants, including polycyclic aromatic hydrocarbons, organochlorine pesticides, polyhalogenated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results suggest the potential applicability of these substrates in detecting chemical contamination in the environment.
对个体动物接触环境污染物进行生化监测的方法具有巨大的潜在用途。各种烷氧基试卤灵是细胞色素P450某些形式的高度特异性底物，其肝脏代谢受到多种环境污染物的高度诱导。因此，在大鼠中，α-六氯环己烷、2,4,5,2',4',5'-六溴联苯、滴滴涕和多氯联苯混合物Aroclor-1254使戊氧基或苄氧基试卤灵的O-脱烷基化诱导超过20倍，而5,6-苯并黄酮、3,4,5,3',4',5'-六溴联苯和Aroclor-1254高度诱导乙氧基试卤灵的代谢。此外，暴露于含低至12 ppm滴滴涕饮食的大鼠，其肝脏苄氧基试卤灵的O-脱烷基化速率增加超过五倍。从暴露于潜在环境污染物的大鼠中获取的9000 xg上清液组分中，这些试卤灵醚的肝脏代谢诱导可能构成包括多环芳烃、有机氯农药、多卤联苯和2,3,7,8-四氯二苯并对二恶英在内的多种污染物存在的有价值诊断指标。这些结果表明这些底物在检测环境化学污染方面的潜在适用性。
