Developmental expression and in situ localization of the phenobarbital- inducible rat hepatic mRNAs for cytochromes CYP2B1, CYP2B2, CYP2C6, and CYP3A1

CJ Omiecinski, C Hassett and P Costa

Department of Environmental Health, University of Washington, Seattle 98195.

In this study we examined the differential hepatic expression of four phenobarbital (PB)-inducible rat cytochrome P450 genes, CYP2B1, CYP2B2, CYP2C6, and CYP3A1. The mRNAs encoding these cytochromes were analyzed in the liver with respect to PB responsiveness, developmental expression, and in situ localization. Utilization of the polymerase chain reaction enabled assessment of specific hepatic mRNA expression patterns during early development that were not detectable with standard Northern blot or slot-blot procedures. The polymerase chain reaction data demonstrated that fetal liver from day 15 of gestation was responsive to the inductive effects of transplacental PB administration. Both constitutive and PB-induced levels of each mRNA increased with increasing developmental age, reaching maximal levels approximately 3 weeks postpartum. An exception to this trend was observed for rats of gestational day 22, which exhibited transiently increased constitutive levels of CYP2B1, CYP2B2, and CYP3A1 mRNAs, such that PB-induced levels were not elevated over those observed in untreated animals. In situ hybridization data, obtained with livers form 6-week postpartum animals, revealed striking differences in regional distributions among the cytochrome P450 transcripts. Whereas patterns of PB-induced expression of CYP2C6 mRNAs were relatively homogeneous across the hepatic lobule, CYP3A1 mRNAs in PB-treated livers demonstrated marked centrilobular localization. These results were in contrast to data obtained previously for PB-inducible CYP2B1 and CYP2B2 mRNAs, which were distributed homogeneously across the hepatic lobule except for cells in the immediate vicinity of the periportal tract.

Volume 38, Issue 4, pp. 462-470, 10/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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