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Comparison of Gene Expression in Preneoplastic and Neoplastic Rat Liver to Adult, Fetal, Regenerating, and Tumor-promoted Liver

Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892

Computer-assisted analysis was performed on the in vitro translation products of polyadenylated RNA samples isolated from normal adult Fischer rat liver and from preneoplastic and neoplastic rat liver samples which were generated by the Solt Farber technique (Solt, D. and Farber, E., Nature 263: 701–703, 1976). The vast majority of the differences in translation products observed throughout the progressive development of hepatocellular carcinoma was quantitative in nature. Importantly, this quantitative heterogeneity first became prevalent at the very early preneoplastic stage of hepatoma formation.

Only 3 consistent qualitative alterations in translation products were observed to be associated with the hepatocarcinogenesis process. The appearance of two new polypeptides of molecular weight and isoelectric point of 32/5.2 and 43/5.1 appeared to be related to an early preneoplastic event in hepatoma development and the transition from a preneoplastic to a neoplastic state, respectively. Importantly, these new polypeptides were not observed in the in vitro translation products generated from fetal or regenerating liver samples or from liver samples which were chronically treated with phenobarbital or terachlorodibenzo-p-dioxin. One translation product (located at 35/6.6) of normal adult, fetal, and regenerating liver RNA samples was undetected in all preneoplastic, neoplastic, phenobarbital-, and terachlorodibenzo-p-dioxin-treated liver RNA translation products. The possibility exists that the specific loss of this gene product may promote the development of the transformed phenotype.

¹ Current address: Department of Experimental Therapy, Wellcome Research Laboratories, 3030 Cornwallis Road, Research Triangle Park, NC 27709. To whom correspondence should be addressed.

² Current address: Subcommittee on Investigations and Oversight, Committee on Science, Space, and Technology, United States House of Representatives, Washington, DC.

Received 10/20/87. Revised 1/11/88. Accepted 1/26/88.