[Modulation of mRNAs P450 and hepatocarcinogenesis promotion].
The adaptive response of the liver to phenobarbital is characterized by a strong cell hypertrophy and coordinate induction of specific P450 forms (IIB1, 2; IIC7, IIIA1). The pattern of active mRNA is significantly changed, demonstrating the establishment of PB phenotype. Employed as a promoting agent in experimental hepatocarcinogenesis, PB triggers a significantly different, uncoordinated response. Only P450 IIB1 is positively modulated while P450 IIC7 mRNA becomes repressed. Mechanisms underlying the differential P450 adaptative response to PB in the initiated versus non-initiated liver are discussed in the light of both the importance of epigenetic events and the possible role of P450 mono-oxygenases in hepatocarcinogenic promotion by PB.
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
M C
MC
Lechner
V L
VL
Ribeiro
D
D
Henrique
M
M
Barroso
M M
MM
Cravino
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D010634:Phenobarbital / Q000494:pharmacology*; D010641:Phenotype; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats
D002273:Carcinogens; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital
Modulation des mRNAs P450 et promotion de l'hépatocancérogenèse.