Strain differences in susceptibility to 2-acetylaminofluorene and phenobarbital promotion of hepatocarcinogenesis: immunohistochemical analysis of cytochrome P-450 isozyme induction by 2-acetylaminofluorene and phenobarbital.

Strain differences in the expression of cytochrome P-450 isoenzymes (P-450s) during enhancement of hepatocarcinogenesis by 2-acetylaminofluorene (2-AAF) and phenobarbital (PB) were investigated immunohistochemically using monoclonal antibodies against phenobarbital (PB) (APF3) or 3-methylcholanthrene (3-MC) (APH8) inducible P-450s. LEW, SD, WBN, F344, SHR, NAR, Wistar and ODS rats were studied, the first five strains proving to be less susceptible to 2-AAF induction of APH8 while responding strongly to the promoting influence of this chemical, as reported previously. The other three strains, NAR, Wistar and ODS, demonstrated greater inducibility, this correlating with an observed resistance to promotion by 2-AAF. PB administration was not associated with any strain difference in APF3 cytochrome P-450 inducibility except in the ODS rat, in which its effects were minimal. The results provide direct evidence that differential expression of cytochrome P-450 species plays a major role in determining responsiveness to hepatocarcinogenesis-promoting agents such as 2-AAF.

2‐acetylaminofluorene

diethyl‐nitrosamine

phenobarbital

cytochrome P‐450

glutathione S‐transferase placental form

partial hepatectomy