Suppression of natural killer and lymphocyte functions associated with carcinogen-induced premalignant hyperplastic...

The effects of chemical carcinogenesis to produce premalignant hyperplastic nodules in rat liver on concomitant immune function were studied. Induction of hyperplastic nodules in Fischer rats was accomplished using a combined regimen of diethylnitrosamine, 2-acetylaminofluorene, and partial hepatectomy. Hyperplastic nodules were detected in carcinogen-treated rats from 5 to 23 weeks as confirmed by gross pathology, histopathology, and significantly elevated liver gamma-glutamyltransferase activity. Suppression of natural killer activity of either peritoneal or peripheral blood lymphoid, but not splenic, cells for YAC-1 target cells occurred during 5 to 20 weeks in carcinogen-treated rats. Spleen and blood lymphocyte mitogenic responses to concanavalin A and pokeweed mitogen were also suppressed at most intervals from 8 through 20 weeks. Control groups given individual carcinogen or partial hepatectomy alone or in dual combination were not suppressed in their immune function and failed to develop hyperplastic foci or changes in liver gamma-glutamyltransferase. Our findings indicate that immunosuppression of natural killer and lymphocyte mitogenic functions occurs for a protracted period concurrently with the development of the premalignant hyperplastic state in rat liver. The data suggest a potential role for immune competency during the onset of malignant neoplasia.