Azaserine carcinogenesis: Organ susceptibility change in rats fed a diet devoid of choline

In rats, azaserine is primarily a pancreatic carcinogen and only induces hepatomas with a very low incidence. We have investigated the effects of feeding a choline‐devoid (CD) diet upon the carcinogenicity of azaserine. Groups of male Wistar rats were fed a CD or a choline‐supplemented (CS) diet. Azaserine (30 mg/kg in 2 ml of saline) was injected IP twice a week for the first 4 weeks, and once a week thereafter, for a total of 14 injections. Control groups were fed the CD or CS diet and were injected similarly with saline. Four to seven animals from each group were killed, 1, 4 and 6 months after the first azaserine injection, and the liver and pancreas were examined histologically. None of the control animals fed the CD or CS diet and given saline injections developed tumors of the liver or pancreas. No hepatomas were observed in 12 rats fed the CS diet and treated with azaserine. On the other hand, 3 of 5 and 5 of 7 rats killed after 4 and 6 months, respectively, of treatment with azaserine and the CD diet showed multiple hepatomas. Rats treated with azaserine developed multiple atypical acinar cell nodules (AACN) of the pancreas after 4 months irrespective of whether choline was present or absent in the diet. However, the number of AACN in rats fed the CD diet was significantly smaller than in rats fed the CS diet. It is concluded that a diet devoid of choline changes the organ susceptibility to the carcinogenic action of azaserine, enhancing hepatocarcinogenesis and reducing the action of the carcinogen on the pancreas.