A Review of the Incidence and Coincidence of Uterine and Mammary Tumors in Wistar and Sprague-Dawley Rats Based on the RITA Database and the Role of Prolactin

Author:

Harleman Johannes H.1,Hargreaves Adam1,Andersson Håkan2,Kirk Sarah1

Affiliation:

1. Astra Zeneca, Safety Assessment, Mereside Alderley Park, Macclesfield, UK

2. Astra Zeneca R&D, Sodertalje, Sweden

Abstract

Wistar rats are frequently selected for use in carcinogenicity studies because of their advantageous survival rate, which is more favorable than other strains such as the Sprague-Dawley (SD) strain. Uterine and mammary tumors are relatively common spontaneous neoplasms of both strains. We examined the incidence and coincidence of uterine tumors and mammary tumors in control animals of both strains within the RITA database. There was a strong inverse relationship between these tumor types in Wistar rats ( p < .001). A less strong relationship was present in SD rats ( p = .057). This association is likely to be related to prolactin. A short review of the role of prolactin in rats is given. These results are also discussed in the background of nonspecific toxicity at high dose levels in carcinogenicity studies above MTD levels resulting in reduction in body weights of >10%.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

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