HISTOCHEMICAL INVESTIGATIONS OF CARCINOGENESIS IN RAT LIVER AFTER CONTINUOUS APPLICATION OF DIETHYLNITROSAMINE

Female rats (Sprague-Dawley) were periodically injected with one of four doses (2.8 mg/kg to 14 mg/kg) of diethylnitrosamine. Almost all liver carcinomas that appeared after months lacked glucose-6-phosphatase as measured histochemically. At all doses clearly delineated islands of cells without glucose-6-phosphatase were observed long before carcinomas appeared. These islands can be distinguished from normal hepatocytes only histochemically. The islands appear at all four doses levels after a total amount of diethylnitrosamine between 210 and 260 mg/kg has been administered. Thus, the first approximation is: c(concentration) ·t(time)=const. Periodic histochemical examination indicates that glycogen is accumulated in the islands lacking glucose-6-phosphatase. This glycogen is no longer responsive to fasting, but usually disappears, later; the cytoplasm becomes increasingly basophilic, after which cell divisions become more frequent. With the appearance of an atypical cell arrangement, the picture of the carcinoma is complete. Striking is the frequent appearance of islands in a 60° sector around the central vein. © 1969 Springer-Verlag.