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ESTABLISHMENT OF TWO RAT HEPATOMA CELL STRAINS PRODUCED BY A CARCINOGEN INITIATION PHENOBARBITAL PROMOTION PROTOCOL
Citation:
Novicki, D., R. Jirtle, AND G. Michalopoulos. ESTABLISHMENT OF TWO RAT HEPATOMA CELL STRAINS PRODUCED BY A CARCINOGEN INITIATION PHENOBARBITAL PROMOTION PROTOCOL. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-83/217.
Description:
Primary tumor formation was induced in a two-thirds partially hepatectomized rat by a single low dose (70 mg/kg of diethylnitrosamine followed by chronic phenobarbital administration (0.1 g/100 ml drinking water). The primary tumors fragments into the inguinal region of syngeneic recipients. The fourth pass was by injection of tumor cells directly into the livers of recipient rats. Several weeks later, the tumor containing rat livers were subjected to collagenase perfusion. Two cell lines emerged from tissue culture of the cells isolated by perfusion. Each cell line was cloned by serial dilution. Cells JM1 and JM2 were tumorigenic when injected into syngeneic rats. The tumors, which arose from injected cells strains, exhibited several characteristics of hepatocellular carcinoma. Morphology was examined by light and electron microscopy. Histochemical studies of JM1 and JM2 cells grown in vitro and in vivo were done. The levels of tyrosine aminotransferase and three microsomal enzymes of importance to drug and carcinogen metabolism were investigated.