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J.Health Sci., 48(6), 514-519, 2002
Effect of Chlorinated Ethylenes on the Expression of Rat CYP2C
Takayuki Nakahama,* Masaki Mizuno, Minori Sekiguchi, Hiroki Sakamaki, and Yoshio Inouye
School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
Chlorinated ethylenes (CEs) are known to be metabolized by CYP2C as well as CYP2E1 and CYP2B. The effects of CEs on the expression of the rat CYP2C gene in the liver and lung were comparatively studied in terms of the enzyme activity, and protein and mRNA contents. Tetrachloroethylene (PCE), trichloroethylene (TCE), and 1,1-dichloroethylene (1,1-DCE) were injected at 0.5g/kg i.p. into male 7-week-old Wistar rats individually or in combination with phenobarbital (PB). The expression of CYP2C mRNA showed organ-specific properties without being detectable in the lung under the assay conditions employed in the present study. Individual CEs had no effect on the enzymatic activity of CYP2C estimated by 2alpha-hydroxylation of testosterone (2alpha-TSH), whereas PB markedly enhanced the enzymatic activity in the liver but not the lung microsomes, although it was highly susceptible to the suppressive effect of 1,1-DCE. A down-regulation of pulmonary enzyme activity was observed with PCE by an unknown mechanism when the animals were treated simultaneously with PB. 1,1-DCE was found to inhibit the expression of hepatic mRNA irrespective of the coexistence of PB, and the same was true for CYP2C protein in the same organ to a lesser extent. In an analogy to our previous findings with other xenobiotic-metabolizing CYP forms such as CYP2B1/2 and CYP2E1, a potent suppressive effect of 1,1-DCE was observed with the maximum around 18 hr after the treatment on both constitutive and PB-induced expression of CYP2C.
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