The incidence, pathology and transplantation of hepatomas in CBA mice

Abstract

At intervals over the whole range of their natural life span of about 2 1/2 yr, 275 male CBA/Birmingham mice including 84 mice over 80 wk of age were autopsied. Body weight increased progressively up to 30 wk of age when a plateau value of 30-40 g was attained. Subsequent to 80 wk a slight, progressive decrease was observed. The thymus showed a profound increase in size from about 5 mg at birth to approximately 60 mg by the 3rd wk. Thereafter, the weight of the thymus decreased, rapidly at first, to reach 20-30 mg by 15 wk of age. The thymus weight decreased more slowly to around 10 mg by the 80th wk. The spleen weight reached a plateau value of 50-60 mg by 4 wk and this was maintained until the 80th wk. In mice older than 80 wk varying degrees of splenomegaly were observed. Histologically, the areas of white pulp in these spleens were prominent, suggestive of an ongoing immune response. It was possible to associate this splenomegaly with the appearance of gross and microscopic evidence of hepatomas. No hepatomas were observed prior to 80 wk, but between 80 and 120 wk the incidence increased progressively; and all mice whose age at autopsy exceeded 120 wk had hepatomas. Histologically the hepatomas showed marked nuclear pleomorphism with occasional mitotic figures. Thrombi, areas of avascular necrosis and collections of inflammatory cells were observed. The tumor metastasized to the lung in 12% of cases. The doubling time of the hepatoma in situ was estimated as 1.6 wk (range 1.3-1.8 wk). These hepatomas were transplantable and grew with a doubling of 2.25 wk in syngeneic adult recipients. To test if the more rapid progressive growth of the tumor in situ in old CBA mice might have resulted from a breakdown in immunological surveillance the same tumor was transplanted simultaneously to a group of young and old recipients. The tumor grew more slowly (doubling time, 2.5 wk) in the old recipients. This result would not appear to support the hypothesis of a prolonged breakdown of immunological surveillance as the cause of the progressive increase in the incidence and growth of these tumors in situ in old mice.