Transplacental induction of cytochromes P-450IA1 and P-450IA2 by polycyclic aromatic carcinogens: TCDD-binding protein level as the rate-limiting step.

Abstract

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.