Lack of carcinogenicity and increased survival in F344 rats treated with 5-fluorouracil for 2 years

The carcinogenicity of 5-fluorouracil (5-FU), a compound employed as an ant ineoplastic drug, was investigated in F344 rats of both sexes. 5-FU was adm inistered to groups of 50 male and 50 female rats ad lib, for 104 weeks, ad ded to drinking water at concentrations of 0 (control), 62 and 125 ppm, the se dose levels being selected on the basis of results of a 13-week subchron ic toxicity study. Body weight gains were slightly depressed in the 125 ppm group of both sexes. While not statistically significant in females, final survival rates at week 111 in the 125 ppm group of both sexes were higher than those in the control group, suggesting an ability of 5-FU to prolong t he lifespan. Histopathologically, a decreased incidence of Islet cell adeno mas in males and increased incidences of pituitary gland adenomas and pheoc hromocytomas in females were observed in the 62 ppm group without dose depe ndence, There was no significant induction of any other neoplastic or non-n eoplastic lesions. These results indicate a lack of carcinogenicity of 5-FU under the present experimental conditions using rats. (C) 2000 Elsevier Sc ience Ltd. All rights reserved.