The immune system during the precancer period: naturally-occurring tumor reactive monoclonal antibodies and urethane carcinogenesis

Abstract

Previous results obtained in our laboratory suggested that natural antibodies reactive with L5178Y lymphoma cells play a role in the induction of lung tumors by the chemical carcinogen urethane. In order to characterize some of the naturally-occurring L5178Y reactive antibodies we prepared hybridomas that secreted natural monoclonal IgM antibodies reactive with L5178Y lymphoma cells. In the present study we characterized some of these antibodies and provided further proof as to their role in urethane carcinogenesis. One hybridoma secreted a cytotoxic antibody that reacted only with mouse lymphoma cell lines. Other non-cytotoxic monoclonal L5178Y-reactive antibodies showed various degrees of cross-reactivity with syngeneic, allogeneic and xenogeneic cells of normal or malignant origin. One of these antibodies reacted much better with activated T cells than with resting ones. Four groups of mice were treated with urethane. Three groups were injected twice a week during 5 months with different IgM preparations of natural monoclonal antibodies. The mice in the fourth group were not treated with IgM and served as controls. Five months after the urethane treatment the mice were sacrificed and the number of tumor foci in the lungs of each mouse was determined. The results show that the group treated with the cytotoxic monoclonal antibody 1.80 had a significant decrease, while the group treated with the IgM myeloma protein 104E had a significant increase in the number of tumor foci compared to urethane-treated mice that did not receive any IgM treatment. The tumor incidence in the group treated with the 104E IgM was significantly higher than that in the control group.