Expression of CYP3A7, a human fetus-specific cytochrome P450, in cultured cells and in the hepatocytes of p53-knockout mice.
CYP3A7 is a major form of cytochrome P450 in human fetal livers. To elucidate toxicological significance of CYP3A7 in fetal livers, CYP3A7 cDNA was introduced into Chinese hamster lung (CHL) cells. Transformants carrying the CYP3A7 gene were more sensitive to mycotoxins than parental CHL cells. In additional studies, we established a hepatocyte cell line from CYP3A7-transgenic/p53-knockout mice. In hepatocyte cells from CYP3A7-transgenic/p53-knockout mice, CYP3A7 mRNA was expressed and the catalytic activity of CYP3A7 protein was detected. The cells are expected to show cytotoxicity to mycotoxins and teratogens. These cell lines provide a valuable panel for studying the fetal toxicities of chemicals in humans.
Kamataki
T
T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Hashimoto
H
H
Shimoji
M
M
Itoh
S
S
Nakayama
K
K
Hattori
K
K
Yokoi
T
T
Katsuki
M
M
Aizawa
S
S
D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D005333:Fetus / Q000201:enzymology*; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout
D003577:Cytochrome P-450 Enzyme System