Pränatale Induktion von hepatocellulären Glykogenspeicherarealen und Tumoren bei Mäusen durch Äthylnitrosoharnstoff

Pregnant C57/Bl6 mice received a single dose of 60 mg/kg bw. ethylnitrosourea i.p. at the 16th day post coitum. The livers of 134 (65 ♂, 69♀) offspring of the treated animals and 131 (63 ♂, 68♀) offspring of untreated controls were investigated by histochemical, electronmicroscopical and biochemical methods at different intervals after birth. Up to 10 weeks no clearcut differences could be detected between the livers of 36 experimental and 29 control animals. 15–20 weeks after birth 8 of 29 experimental animals showed hepatic glycogen storage areas demonstrated histochemically. In 1 mouse a neoplastic hepatic nodule rich in glycogen was found. Biochemically significant differences in the hepatic glycogen content of experimental and control animals could not be detected at that time. 26 weeks after birth 13 of 15 experimental animals exhibited hepatic glycogen storage areas, while 3 animals had developed neoplastic nodules. Biochemically the hepatic glycogen content of the male experimental animals was significantly higher than that of the male controls. Electronmicroscopically the accumulated glycogen was found predominantly in the cytoplasmic matrix, sometimes in close contact with membranes of the agranular ER. Many cells of the neoplastic nodules were characterized by the appearance of liposomes and large spongy bodies in the dilated cisternae of the granular ER. 58–78 weeks after birth 10 of 54 animals showed hepatic glycogen storage areas, 26 neoplastic nodules and 26 hepatocellular carcinomas. In the corresponding control group 1 neoplastic nodule was observed. The results indicate that the development of hepatocellular tumors induced prenatally in mice is closely related to a focal hepatic glycogenosis.