Fischer 344系ラットにおけるコリン欠乏およびコリン添加アミノ酸食の長期投与による毒性と発癌性

Abstract

The present study assessed toxicologic and carcinogenic effects of a long- term administration of semisynthetic, choline-deficient, L-amino acid-defined (CDAA) and choline-supplemented, L-amino acid-defined (CSAA) diets in Fischer 344 (F344) rats. Male and female F344 rats, 5 weeks old, were fed the CDAA or CSAA diet or a conven- tional laboratory chow, and sacrificed at the end of week 52 and by the end of week 104. All organs were excised on sacrifice and histologically examined. The following results were obtained. 1. Hepatocellular carcinomas (HCCs) were induced with high incidence in male rats fed the CDAA diet. HCC was induced in the background presence of fatty liver and cirrhosis, through a progression sequence starting from eosinophilic altered hepatocellular focus, then hepatocellular adenoma, and carcinoma-in-adenoma. 2. HCCs were also induced in female rats fed the CDAA diet with the lower incidence than in male case. 3. The CDAA diet suppressed the induction of testicular interstitial cell tumors and pituitary adenomas in males. Both of the CDAA and CSAA diets promoted the induction of mammary fibroadenomas in females. 4. The CDAA diet induced intestinal lacteal dilatations in both genders, and promoted the induction of nephropathies in both genders and nephrocalcinoses in males. Both of the CDAA and CSAA diets promoted the induction of pancreatic altered acinar cell foci plus acinar cell hyperplasias, forestomach squamous cell hyperplasias and thyroidal C-cell hyperplasias in both genders and nephrocalcinoses in females. It is thus indicated that the CDAA diet is hepatocarcinogenic toward both of male and female F 344 rats and modifies the induction of various spontaneous lesions. In addition, the CSAA diet can also modify the induction of some spontaneous lesions. Assessments for the detailed machanisms underlying not only hepatocarcinogenesis but also modification of the induction of various other lesions are warranted in rats fed the CDAA diet.