The age-related incidence of spontaneously occurring neoplasms and degenerative diseases in the F344 inbred rat strain was established from the histologic examination of tissues from 160 male and 192 female rats kept throughout their natural life-span. The most common neoplasms were leukemias (25%), mammary tumors (females, 40.6%; males, 23.1%), pituitary adenomas (females, 35.9%; males, 23.8%), and testicular interstitial cell tumors (males, 85%). Various less common neoplasms were observed: thyroid interstitial cell tumors, adrenocortical adenomas, carcinomas of the genitourinary tract, representative central nervous system tumors, pheochromocytomas, and tumors of mesodermal origin including mesotheliomas, myoblastomas, fibromas, and fibrosarcomas. Multiple tumor types were found in 176 of the rats; metastatic tumors were uncommon. Degenerative diseases including myocardial degeneration and nephrosis were often observed. The incidence rate of these neoplasms and degenerative diseases generally increased with advancing age of the animals.

Administration of 40 ppm diethylnitrosamine (DENA) in the drinking water for 10 weeks to male Fischer rats led to hepatocellular carcinoma in 100 percent with metastasis to the lung in 40 percent, of the animals living for the full experimental period of 20 weeks. Concurrent feeding of phenobarbital and DENA for 10 weeks produced cancer of the liver in 77 percent of the animals, but only 9 percent had metastases in the lung. A brief regimen of DENA for 4 weeks, followed by 16 weeks of observation, induced cancer of the liver in only 13 percent of the rats. Administration of phenobarbital, begun 1 week after cessation of DENA intake and terminated at week 20, led to liver cancer in 64 percent of the rodents. Hydroxyurea had no effect on this enhancement. Treatment with a purified gamma fraction of antilymphocytic serum after the DENA did not influence the outcome. Thus phenobarbital given together with DENA reduced the severity of the carcinogenic process, but when it was given after the hepatocarcinogen, it increased the effect.

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