Lack of carcinogenicity and increased survival in F344 rats treated with 5-fluorouracil for two years.
The carcinogenicity of 5-fluorouracil (5-FU), a compound employed as an antineoplastic drug, was investigated in F344 rats of both sexes. 5-FU was administered to groups of 50 male and 50 female rats ad lib. for 104 weeks, added to drinking water at concentrations of 0 (control), 62 and 125 ppm, these dose levels being selected on the basis of results of a 13-week subchronic 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 the lifespan. Histopathologically, a decreased incidence of islet cell adenomas in males and increased incidences of pituitary gland adenomas and pheochromocytomas in females were observed in the 62 ppm group without dose dependence. There was no significant induction of any other neoplastic or non-neoplastic lesions. These results indicate a lack of carcinogenicity of 5-FU under the present experimental conditions using rats.
Toyoda
K
K
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan. ktoyoda@nihs.go.jp
Shibutani
M
M
Sato
H
H
Uneyama
C
C
Takahashi
M
M
Hayashi
Y
Y
Hirose
M
M
D000236:Adenoma / Q000453:epidemiology / Q000517:prevention & control; D007516:Adenoma, Islet Cell / Q000453:epidemiology / Q000517:prevention & control; D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000633:toxicity*; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000633:toxicity*; D015994:Incidence; D008017:Life Expectancy; D008297:Male; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D010673:Pheochromocytoma / Q000453:epidemiology / Q000517:prevention & control; D010911:Pituitary Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil