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High Incidence of Hepatocellular Carcinomas Induced by a Choline Deficient L-Amino Acid Defined Diet in Rats¹

Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan

The carcinogenicities of a choline deficient L-amino acid defined (CDAA) diet and a semipurified choline deficient diet were comparatively examined. A total of 60 male Fischer 344 rats, 6 weeks old, were divided into 5 experimental groups each consisting of 12 rats. Group 1 received the CDAA diet chronically to the end of the 52-week experiment while Group 2 was given the same diet for the first 24 weeks and then a basal diet for the following 28 weeks. Groups 3, 4, and 5 received a choline supplemented L-amino acid defined diet, the semipurified choline deficient diet, and a semipurified choline supplemented diet, respectively, throughout the experimental period. All surviving rats were subjected to complete macroscopic examination at Week 52. Histopathologically diagnosed hepatocellular carcinomas were induced in Group 1 at an incidence of 100%; multiple metastatic nodules were seen in the lungs of one of the animals. Hepatocellular carcinomas were also induced in Group 4 rats at a significantly lower incidence of 20%. No hepatocellular carcinomas were observed in rats in Groups 2, 3, and 4. The results indicate that the CDAA diet exerts more potent carcinogenicity for the livers of rats than does the semipurified choline deficient diet. However, limited exposure for 24 weeks may have not been sufficient for hepatocellular carcinoma induction by the CDAA diet at Week 52 although a high incidence of hyperplastic nodules and slight cirrhosis were evidence of persistent lesions.

¹ This work was supported in part by Grants-in-Aid for Cancer Research 1–22 and 3–11 and by a Grant-in-Aid for the Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan.

² To whom requests for reprints should be addressed.

Received 3/26/92. Accepted 7/ 8/92.

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