Spontaneous tumor incidence in rasH2 mice: review of internal data and published literature.

Alternate transgenic mouse models are accepted as replacements for the standard carcinogenicity mouse bioassay by regulatory agencies with a companion 2-year rat bioassay. The slower rate of industry acceptance of these shorter transgenic mouse cancer bioassays has been due to lack of historical data and diagnostic criteria, and the use of nonstandardized terminologies in published data. To address these issues, especially that of generating a large historical database, a retrospective analysis of the spontaneous tumor incidences in rasH2 mice from internally sponsored 6-month carcinogenicity studies was compared to the published literature. Incidences of common spontaneous tumors (incidences > 1%) observed in these studies were lung bronchiolo-alveolar adenomas (mean 3.9-9.9%; range 0-18%), lung bronchiolo-alveolar adenocarcinomas (mean 1.4-2.4%; range 0-5%), splenic hemangiosarcomas (mean 3.0-3.9%; range 0-17%), cutaneous squamous cell papillomas (mean 1.1-1.2%; range 0-4%), Harderian gland adenoma (mean 0.8-1.2%; range 0-4%), and hepatocellular adenomas (mean 1.8%; 0-9% in males only). The remarkable similarity in the tumor incidences in multiple rasH2 studies over a decade and the observed stability of the inserted human gene are important indicators of the minimal drift in this model. Overall, the historical control data for spontaneous neoplasms should assist in the interpretation of future rasH2 mouse studies.