EXPRESSION OF THE CYTOCHROME-P4502E AND 2B-GENE FAMILIES IN THE LUNGS AND LIVERS OF NONPREGNANT, PREGNANT, AND FETAL HAMSTERS

Members of the cytochrome P4502E and 2B gene families have been implicated in the activation of nitrosamines to reactive species capable of binding to cellular macromolecules and initiating tumor formation in various rodent species. This study was initiated to determine the relative prevalence of these isozymes and their response to ethanol during pregnancy and late gestation. Nonpregnant and pregnant hamsters were given a 10% ethanol solution in their drinking water for 10 days (gestation days 5-15) prior to being killed. RNA blot analysis of liver and lung tissue from nonpregnant, pregnant, and fetal hamsters demonstrated tissue-specific expression of CYP2E and 2B in adult and fetal animals. The levels of RNA expression of both P450s in fetal hamsters were < 30% of nonpregnant adult values. In pregnant hamsters, the hepatic levels of CYP2E and 2B RNAs were decreased compared to nonpregnant animals. In contrast, the pulmonary levels of CYP2B RNA were increased in pregnant versus nonpregnant hamsters, while no effect of pregnancy on the levels of CYP2E RNA was seen. Although rats contain a single CYP2E1 gene transcript, Northern analysis demonstrated the presence of 1.8 and 2.8 kb bands in both liver and lung tissue of the hamster. Pretreatment with ethanol had little effect on the levels of either P450 RNA species in the lungs or livers of nonpregnant, pregnant, and fetal hamsters. These results demonstrate differences in the levels of expression of members of the CYP2E and 2B gene families during pregnancy and late gestation compared to nonpregnant adult hamsters. Fetal animals, like the adults, apparently respond to ethanol treatment by altering the levels of these P450 isozymes at the post-transcriptional level.