Abstract
An enzyme involved in the metabolic activation of thalidomide has been investigated using embryo fibroblast proliferation as a marker. Thalidomide (30 μM) induced-suppression of embryo fibroblast proliferation was detected in the presence of liver microsomes from rabbit but not from mouse. The addition of a selective inhibitor of CYP1A, α-naphthoflavone (4 μM), or furafylline (4 μM), to the incubation mixture abolished the thalidomide-induced suppression. Furthermore, addition of anti-rat CYP1A1 antibody also resulted in inhibition of suppression. The thalidomide-induced suppression was also observed with the microsomal system from human HepG2 cells pretreated with 3-methylcholanthrene (10 μM) but not from those pretreated with the vehicle. Both CYP1A1 and CYP1A2 proteins were detected in the rabbit liver microsomes by immunoblot analyses, but only CYP1A2 protein was detected in the mouse liver microsomes. In addition, CYP1A1 protein was detected in microsomes from HepG2 cells pretreated with 3-methylcholanthrene but not with the vehicle. These results strongly suggest the involvement of CYP1A1 in the thalidomide-induced suppression of embryo fibroblast proliferation.
Footnotes
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This study was supported by a Grant-in Aid from the Ministry of Education, Science, and Culture, Japan; and the Human Science Foundation.
- Abbreviations used are::
- mEH
- microsomal epoxide hydrolase
- SOD
- superoxide dismutase
- GD
- gestational day
- DMSO
- dimethyl sulfoxide
- P450
- cytochrome P450
- OD
- optical density
- Received June 17, 2002.
- Accepted January 6, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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