The stability of historical control data for common neoplasms in laboratory rats and the implications for carcinogenic risk assessment.

摘要

Time-related changes in the incidences of spontaneous neoplasms in skin (fibroma and keratoacanthoma), thyroid (C-cell and follicular cell adenomas/carcinomas), uterus (stromal polyp), testes (Leydig cell tumor) and hemolymphoreticular system (mesenteric lymph node hemangioma and malignant granular lymphocytic leukemia) were assessed statistically in Wistar, Sprague-Dawley and F344 rats employed by the BASF, Germany and major European contract research organizations over the last 20 years. Negative trends (5 out of 80 cases) were observed for skin fibromas in F344 males, for follicular cell adenomas in Han Wistar females and in Sprague-Dawley males and females, and for follicular cell carcinomas in Sprague-Dawley males. Positive trends (8 out of 80 cases) were observed for skin keratoacanthomas in Han Wistar males, for C-cell adenomas in BASF Wistar males and females, for stromal polyps in Han Wistar and Sprague-Dawley females, and for mesenteric lymph node hemangiomas in Han Wistar and Sprague-Dawley males and in BASF Wistar females. In 67 out of 80 cases there were no statistically significant trends. Tumor drift was not common but occurred far more often in outbred rat strains (Wistar and Sprague-Dawley) than in the inbred rat strain (F344). This observation suggests that tumor predisposition is genetically determined, that tumor drift is primarily caused by genetic drift and that non-genotoxic carcinogens operate by facilitating the expression of tumor predisposition in target cells.