High Background Incidence of Spontaneous Subcapsular Adrenal Gland Hyperplasia of Tg.rasH2 Mice Used in 26-week Carcinogenicity Studies.

The Tg.rasH2 model was accepted by regulatory agencies worldwide for 26-week carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice in 2003. Several references documenting spontaneous nonneoplastic findings and incidences of spontaneous tumors in the Tg.rasH2 mice have been published. The purpose of this publication is to add adrenal gland subcapsular hyperplasia to the database pertaining to spontaneous lesions noted in Tg.rasH2 mice, review physiology related to this finding, and discuss its significance. The incidence of spontaneous subcapsular adrenal gland hyperplasia was determined in control Tg.rasH2 mice from nine 26-week carcinogenicity studies carried out within the last 5 years at two contract research organizations. Incidence of this finding ranged from 56% to 79% in males and 88% to 100% in females, with an incidence average of 62% in males and 93% in females. Adrenal gland subcapsular hyperplasia is a common finding in male and female Tg.rasH2 mice that did not progress to neoplasia in Tg.rasH2 mice. In general, it tends to be more frequent and severe in females in comparison to males.