Function and its Application of Cytochrome P450: To Achieve Drug Metabolism Studies for Humans

Abstract

The properties of cytochrome P450 varies among molecular forms over animal species. Thus, such a variation is believed to result in the species differences in drug metabolism. We have performed research to predict drug metabolism in humans. We purified and cloned forms of cytochrome P450 from animals and humans, and clarified the properties by expression in hetelrologous system. Among them, CYP3A7 is a form of cytochrome P450 present specifically in human fetal livers. First, we analyzed 5'-upstream region to know elements involved in the respective fetal and adult specific expression of CYP3A7 and CYP3A4. We found that there were two elements which might cause the fetal and adult specific expression of these cytochromes. To answer a question if cytochrome P450 acts in vivo as estimated by in vitro studies, we established transgenic mice carrying CYP3A7 gene. When the transgenic mice were treated with aflatoxin B₁, DNA damage as well as aflatoxin B₁ DNA adduct occurred only in organs in which CYP3A7 was expressed.