Effects of Tetrachloroethylene and 1,1,1-Trichloroethane on the Expression of P450 Isoforms in Rat Lung and Liver

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Tetrachloroethylene (PCE) and 1,1,1-trichloroethane (1,1,1-TCA) were administered intraperitoneally at a moderately toxic dose of 1 g/kg/d for three consecutive days to male and female Wistar rats weighing about 200g (7 weeks old). The agents were given alone or simultaneously with phenobarbital (PB, 80mg/kg/d) and the animals were sacrificed 24h after the last treatment. Microsomal fractions prepared from both lungs and livers were tested for the monooxygenase activity and protein content of four cytochrome P450 (CYP) isoforms, i.e., CYP1A, 2B, 2E1 and 3A. As far as the monooxygenase activity was concerned, CYP1A, 2E1 and 3A but not 2B were constitutive in liver while only CYP2B was detected in lung. PCE suppressed significantly pulmonary CYP2B and hepatic CYP2E1 but enhanced hepatic CYP1A. In contrast, 1,1,1-TCA suppressed hepatic CYP2E1 under the conditions used. Although PB induced hepatic CYP2B and enhanced CYP1A several-fold, it had no effect on CYP2E1 and 3A, as well as pulmonary CYP2B. The effects of PCE and 1,1,1-TCE on CYP isoforms in microsomal fractions prepared from PB-cotreated animals were also studied comparatively in terms of sex and organ. The response of pulmonary enzymes to both chemicals was the same as that of PB-untreated animals. As far as PB-induced hepatic CYP2B was concerned, PCE was suppressive while 1,1,1-TCA showed a degree of potentiation. Furthermore, in the case of CYP1A a sex difference was noted in the response to these chemicals. As far as the protein levels of CYP isoforms were concerned, they were generally proportional to the enzyme activities.
公益社団法人日本薬学会の論文
2000-02-01

Effects of Tetrachloroethylene and 1,1,1-Trichloroethane on the Expression of P450 Isoforms in Rat Lung and Liver

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