Incidence of Neoplasms and Selected Non-Neoplastic Findings in Control and Positive Control Groups in CByB6F1-Tg(HRAS)2Jic Hemizygous (rasH2 TM ) Mouse Carcinogenicity Studies

Abstract

The rasH2^TM mouse model has become the primary alternative to a 2-year mouse carcinogenicity study in safety testing of human pharmaceuticals. In this publication, we present the neoplastic incidence for 2291 control males, 2191 control females, 575 MNU-treated males, 559 MNU-treated females, and 210 urethane-treated males and females in rasH2^TM carcinogenicity studies conducted from 2012 to 2024 as well as survival, body weights, and selected non-neoplastic microscopic findings for control and positive control mice. Inclusion of a positive control group is recommended to ensure regulatory acceptance. Survival of controls at the end of 26 weeks was approximately 96% with similar percentages of survivors in the 13-week urethane-treated positive controls in contrast to a survival percentage of approximately 17% in MNU-treated positive controls. Malignant neoplasms accounted for most early deaths in control and positive control mice. Major neoplasms in control mice included Harderian gland adenomas, bronchioloalveolar adenomas and carcinomas, and splenic hemangiosarcomas, while the predominant neoplasms in MNU-treated mice included squamous cell papillomas and carcinomas of the nonglandular stomach and malignant lymphomas. The percentage of urethane-treated mice developing bronchioloalveolar neoplasms was over 98% in both sexes. When compared to control mice, MNU-treated mice had lower mean body weights while urethane-treated mice had higher mean body weights. Major non-neoplastic findings in control mice were subcapsular cell hyperplasia (51.78% to 89.41%) and skeletal muscle myopathy (77.17% to 80.71%). Other non-neoplastic findings included retinal degeneration in MNU-treated mice (∼87% in both sexes) and bronchioloalveolar hyperplasia in urethane-treated mice (≥53% in both sexes).