Over expression of proto-oncogenes: ki-ras, fos and myc in rat liver cells treated in vitro by two liver tumor promoters: phenobarbital and biliverdin.

Among the liver cell strains established in the laboratory from the liver of 10-day-old rats, some of them (FV) underwent spontaneous neoplastic transformation after a number of subcultures. However, one (Cl3) had maintained a non-transformed phenotype (persistence of contact inhibition, lack of growth in soft agar and of gamma glutamyltranspeptidase activity). These cells were grown either for a short time (48 h) or a longer time (3 weeks) in the presence of two liver tumor promoters: phenobarbital (0.2 x 10(-3) M) or biliverdin (10(-6) M). Total RNA was analysed by dot blot and Northern blot, then hybridized with ki-ras, fos and myc probes, previously labelled with 32P by nick translation. The three oncogenes were well expressed by the two strains but while an over-expression was observed for the Cl3 non-transformed cells when they were grown in presence of phenobarbital or biliverdin, the FV-transformed cells were not sensitive to the two promoters.