SUSCEPTIBILITY OF EXPERIMENTAL AUTOIMMUNE HEPATITIS IN TRANSGENIC MICE OVEREXPRESSING THE C-H-RAS GENE

Results from a recent study of ours have demonstrated the significant role of the wild-type ras gene in the development of hepatocellular ca rcinoma in rasH2 mice having prototype human c-H-ras genes. Chronic ce ll death and regeneration have been considered to work as co-carcinoge ns with wild-type ras gene overexpression in this model. To elucidate a role of gene overexpression in the occurrence of chronic inflammatio n, we tried to induce inflammation in the liver of rasH2 mice by immun izing them with the supernatant of a freshly prepared syngenic liver h omogenate. Immunization resulted in a dense inflammatory infiltrate in the portal tract and focal necrosis with spots of fatty or foamy dege neration in the transgenic mouse liver; however, these observations we re less frequently observed in non-transgenic mouse liver. Monocytes, granulocytes and plasma cell infiltration were observed in the livers of transgenic mice. An immunohistochemical study showed that CD3-posit ive lymphocytes also infiltrated the liver. The inflammatory infiltrat e was still present in the transgenic liver 24 weeks after the last in jection, but little infiltrate was observed at the same time in non-tr ansgenic mice. No hepatic rumours could be produced over the 6 months duration of the study and the results are only preliminary. However, t hese results do suggest that overexpression of wild-type ras is partia lly responsible for the occurrence of autoimmune chronic hepatitis.