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 comparedin fetal and adult rat liver. A single dose of 3-methylcholanthrene(MC) 16 h before death, resulted in a pronounced accumulationof both mRNAs in adult liver. In contrast, treatment of fetuseswith a single dose of MC did not increase the hepatic contentin P-450c and P-450d mRNAs, whereas a 3-day treatment gave riseto a considerable accumulation of mRNAs. The fetal rat livercontent in 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-bindingprotein was extremely low compared to the adult content. Pretreatmentof fetuses with phenobarbital potentiated the inducing effectof MC upon P-450c and P-450d mRNA accumulation in relation tothe duration of pretreatment, as well as increasing the hepaticcontent in TCDD-binding protein. Data strongly suggest thatthe hepatic TCDD-binding protein level is the rate-limitingstep in MC induction of P-450c and P-450d in fetal but not inadult rat liver. In addition, phenobarbital and MC are potentinducers of the TCDD-binding protein in the fetal rat liver.