LEVELS OF MYC, FOS, HA-RAS, MET AND HEPATOCYTE GROWTH-FACTOR MESSENGER-RNA DURING REGENERATIVE CELL-PROLIFERATION IN FEMALE MOUSE-LIVER ANDMALE-RAT KIDNEY AFTER A CYTOTOXIC DOSE OF CHLOROFORM

Chloroform is a liver carcinogen in mice and a kidney carcinogen in ra ts. It is thought to act through a non-genotoxic-cytotoxic mode of act ion. Changes in expression of growth control genes accompanying chloro form-induced cytolethality and regeneration may play a part in the dev elopment of chloroform-induced tumors. In this experiment, we examined the levels of the myc, fos, Ha-ras, met and hepatocyte growth factor mRNA in livers of female B6C3F(1) mice and kidneys of male F-344 rats to detect changes in gene expression following a single, cytotoxic gav age dose of chloroform in corn oil. Poly A(+) RNA was purified from ho mogenates of livers of mice treated with 350 mg/kg chloroform and kidn eys of rats treated with 180 mg/kg chloroform and used for Northern bl ot analysis. Livers of female mice showed large transient increases in levels of myc and fos mRNA while levels of Ha-ras, met and the hepato cyte growth factor gene mRNA remained near control levels. In the male rat kidney, levels of myc mRNA increased after treatment, while level s of mRNA of all other genes examined remained near control levels. Th is pattern of gene expression is consistent with that induced by other cytotoxic carcinogens and suggests that alteration of the myc and fos genes could be involved in the regenerative cell proliferation that u ltimately could play a role in chloroform-induced tumors.