The histochemical localization of alkaline phosphatase during carcinogenesis in rats fed p-dimethylaminoazobenzene.

Greenstein in 1942 found a high content of alka line phosphatase in transplanted rat hepatoma 31 (3). This tumor arose originally in the liver of a male Osborne-Mendel rat and was induced by the basal diet of White and Jackson (16) containing 0.06 percent />-diinethylaniinoazobenzene (DAB) with intermittent addition of 0.5 per cent cystine and 0.5 per cent methionine (17). The enzyme ac tivity was determined with disodium phenylphosphate as substrate. Woodard in 1943 studied the alkaline phosphatase activity of livers of rats fed a diet containing 20 cc. of 3 per cent DAB mixed with 1,000 gin. brown rice and supplemented with carrots (19). Sodium ß-glycerophosphatewas used as substrate (20). It was noted that the average alkaline phosphatase activity, in units per gram of tissue, was 10 times higher in hepatic tumors than in normal liver. An intermediary stage following dye feeding, designated as precancerous, also showed a significant rise in alkaline phosphatase activity above normal liver, but not as high as that of hepatic tumors. The histochemical demonstration of alkaline phosphatase activity has been reported by White, Dalton, and Edwards (17) for rat hepatoma 31 transplants and by Kabat and Furth (5) for pri mary hepatic carcinoma in the rat. The purpose of the present study was to ascertain where the in creased phosphatase activity was localized in (he liver of rats fed DAB and to follow the localization at intervals during the carcinogenic process. A pre liminary report was presented in 1948 (14). The taxonomy of liver tumors induced by DAB has been studied by several investigators, utilizing different basal diets (10, 11, 13, 17, 18). These tumors are complex histologically and are appar-