The alteration of gene expression in rat liver during chemical carcinogenesis.

The effect of the carcinogen 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB) on the gene expression of rat liver was studied. Hybridization analysis with enriched neoplastic liver specific cDNA demonstrated a noticeable change in gene expression during liver carcinogenesis. The effect of 3'-MDAB on liver specific gene expression was also studied with albumin and alpha-fetoprotein (AFP) genes as models. Serum AFP levels increased dramatically during hepatocarcinogenesis. Amounts of AFP mRNA present in polysomal poly(A)mRNA were determined by translation and hybridization experiments. AFP mRNA increased in carcinogen-treated liver as the serum level of AFP increased. Increase of AFP mRNA in liver cytoplasmic RNAs can be detected as early as 18 days after feeding rats 3'-MDAB and reached peaks at 30-40 and 185 days of treatment. AFP serum level and AFP mRNA in liver cytosol decreased dramatically between these peaks, with a small amount of AFP mRNA and serum AFP detectable in rats treated with 3'-MDAB for 100 days. The increase in amount of AFP mRNA was due to an increase in transcription of the AFP gene in livers of rats treated with carcinogen. Only a slight change in serum albumin concentration and albumin mRNA in livers of rats treated with 3'-MDAB was noticed.