Transplacental induction of cytochromes P-450IA1 and P-450IA2 by polycyclic aromatic carcinogens: TCDD-binding protein level as the rate-limiting step.
Induction of cytochromes P-450c and P-450d have been compared in fetal and adult rat liver. A single dose of 3-methylcholanthrene (MC) 16 h before death, resulted in a pronounced accumulation of both mRNAs in adult liver. In contrast, treatment of fetuses with a single dose of MC did not increase the hepatic content in P-450c and P-450d mRNAs, whereas a 3-day treatment gave rise to a considerable accumulation of mRNAs. The fetal rat liver content in 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-binding protein was extremely low compared to the adult content. Pretreatment of fetuses with phenobarbital potentiated the inducing effect of MC upon P-450c and P-450d mRNA accumulation in relation to the duration of pretreatment, as well as increasing the hepatic content in TCDD-binding protein. Data strongly suggest that the hepatic TCDD-binding protein level is the rate-limiting step in MC induction of P-450c and P-450d in fetal but not in adult rat liver. In addition, phenobarbital and MC are potent inducers of the TCDD-binding protein in the fetal rat liver.
Marie
S
S
INSERM U75, CHU Necker, Paris, France.
Anderson
A
A
Cresteil
T
T
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000502:physiology; D008297:Male; D008431:Maternal-Fetal Exchange; D008748:Methylcholanthrene / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism*
D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital