Species: Rat Strain/breeder: Wistar HSD/Win: WU / Harlan-Winkelmann Sex: Female Age: 2 years Study type: Carcinogenicity study Treatment: Test compound admixed to the diet Animal status: Scheduled death Clinical findings: Food consumption reduced to 80% of control values Organ: Uterus with nodule Macroscopic finding(s): Uterus, left horn: nodule, appr. 0.8 cm in diameter; Abdominal cavity: nodule, appr. 0.5 cm in diameter. Unilateral dilatation of the renal pelvis. Staining: H&E Literature: Mohr U (1997) International classification of rodent tumours. Part I: The rat. 9. Female genital system. IARC, Lyon Roe FJC, Lee PN, Conybeare G, Kelly D, Matter B, Prentice D, Tobin G (1995). The Biosure Study: influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in Wistar rats studied for up to 30 months post weaning. Food Chem Toxicol 33 Suppl 1:1-100

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Abstract

Aim of the study
The evaluation of a regulatory type carcinogenicity study revealed an increased incidence of uterine epithelial tumours, mostly adenomas, adenocarcinomas, and squamous cell carcinomas, in high dose group animals. Severe diffuse epithelial hyperplasia, the presumed preneoplastic precursor lesion, was concomitantly increased. Recent studies on the influence of food intake on the incidence of various tumours indicate that food restriction or a retardation in body weight development lead to an increased incidence of uterine tumours.

Materials & methods
To elucidate a possible influence of food restriction and its mechanism on the increased incidence of uterine neoplasms food intake and body weight were set in relation to the incidence of uterine epithelial tumours. Prolactin levels of serum taken in test week 52 were determined by use of a commercial ELISA kit.

Results
In the high dose group food intake was reduced to 88% of control values. This resulted in a mild retardation of body weight development of 14% and a statistically significant reduction of serum prolactin levels in high dose group animals.

Conclusions
The results indicate that mild to moderate reduction of food consumption has led to a slightly decreased body weight development and to a marked influence on the hormonal status of the treated animals. The decreased prolactin levels obviously led to a relatively increased endogenous estrogen stimulation and subsequent development of uterine hyperplasia and tumours. Because prolactin is not luteotropic in primates, it is obvious that this finding has no relevance to man.