Identification of carcinogens by measurement of cell-mediated immunity: I. Immunity induced by rat pancreas and colon carcinogens

Abstract Anti-tumor cell-mediated immunity was used as a measure of exposure to chemical carcinogens. The measurements involved determining the amount of cytotoxicity to cultured X-ray-induced rat small bowel adenocarcinoma cells exhibited by peripheral blood lymphoid-cells isolated from animals exposed to the carcinogens. Cytotoxicity was determined by the release of radioiodinated integral and peripheral proteins of the small bowel cancer cells. The studies indicate that exposures to 1,2-dimethylhydrazine (DMH) which induces colon adenocarcinomas and 7,12-dimethylbenz[ a ]anthracene (DMBA) implants which produce pancreatic adenocarcinomas, can be detected within a 6- to 72-day postexposure interval. Dose response studies of the DMH indicate exposures to as little as 100 μg (1.7 μmol) can be detected within this time interval although this amount is insufficient to produce detectable cancer. The present results further outline the specificity of the assay since it was found that tumors of mesodermally derived tissues (asbestos-induced peritoneal mesotheliomas) and nonspecific injury (70% surgical resection of ileum and jejunum) will not induce cytotoxicity. Our previous studies had shown ectodermal lesions also will not evoke responses; therefore, these findings suggest the measured anti-tumor immunity is specific to carcinogens which interact with entodermally derived tissue. Thus, the findings support our suggestion that measurement of anti-tumor immunity offers a rapid, sensitive, and specific technique for detecting carcinogenic substances.