EFFECT OF ETHANOL AND COCAINE TREATMENT ON THE IMMUNE-SYSTEM OF V-HA-RAS-TRANSGENIC MICE

The objective was to investigate if the presence of the v-Ha-ras oncog ene could induce immune changes different to the ones observed in norm al mice. Therefore, we decided to use Oncomice, the transgenic mice wi th an activated v-Ha-ras oncogene under the control of the mouse mamma ry tumor virus-promoter, and their normal inbred counterparts, FVB mic e. Both strains of mice were fed the Lieber-DeCarli liquid diet with e thanol or the isocaloric control diet and were injected daily with coc aine or saline. The percentage and absolute number of T and B lymphocy tes in the spleen and thymus were determined. The in vitro production of TNF-alpha (tumor necrosis factor-alpha), IL-2 (interleukin-2) and I FN-gamma (interferon-gamma) by spleen cells, and the levels of serum s IL-2R (soluble IL-2 receptor) were also measured. Oncomice fed the Lie ber-DeCarli ethanol diet or receiving either saline or cocaine injecti ons presented a higher tumor incidence than Oncomice receiving the con trol diet. A reduced total number of thymocytes as well as absolute nu mber of cells in all the subsets was found in Oncomice. Moreover, a de creased percentage of CD8(+) cells was also observed in Oncomouse sple ens. These features were even more marked in ethanol-treated Oncomice. Higher serum slL-2R levels were observed in Oncomice, especially in m ice treated with ethanol or cocaine. The results suggest that the onco gene product, P21(ras), plays an important role in dysregulating the i mmune system and hence in favoring tumorigenesis. Copyright (C) 1996 I nternational Society for Immunopharmacology.