Antibody-dependent cell cytotoxicity in chemical-induced rat pancreas and colon cancer

Abstract Antibody-dependent cell cytotoxicity (ADCC) was measured in rats having 1,2-dimenthylhydrazine (DMH)-induced colon and 7,12-dimethylbenz[ a ]anthracene (DMBA)-induced pancreas adenocarcinomas. The ADCC assay consisted of determining the levels of cytotoxicity induced in noncommitted peripheral blood lymphoid cells (PBLC) by the serum of its components as measured by the increased release of radioiodinated peripheral and integral membrane proteins from injured and killed X-ray-induced rat small bowel adenocarcinoma target cells. The serum component responsible for the ADCC appeared to be an immunoglobulin of the IgG class based upon solubility in ammonium sulfate, molecular weight, inactivation by pepsin and reactivity with Protein A. These immune responses were specific for entodermal tissue since serum obtained from those rats having ectodermal (spontaneous-occurring mammary and transplanted prostate) as well as mesodermal (asbestos-induced) lesions did not demonstrate ADCC in the assay. This serum which was lytic in the presence of the PBLC obtained from the rats having the chemically induced lesions was found not to be cytotoxic in itself to the cultured cells of these tumors or in the presence of PBLC to normal kidney epithelial or skin fibroblast cells. The findings suggest that identical or common antigens do exist in cancer cells arising in entodermally derived tissue that are induced by ionizing radiation, and aliphatic and polyaromatic carcinogens which can then stimulate a common antitumor immunity. These results support the concept that measurement of such immune responsiveness will permit sensitive and specific in vivo determination of those environmental substances which induce cancer cells.