Mouse Models for Radiation-Induced Breast Cancer

Abstract

Radiation is a widely known, and prototypical, inducer of genotoxic damage. With every moment of exposure to ionizing radiation, lesions and breaks are induced in the DNA, increasing an individual's lifetime risk of developing cancer. At the same time, radiation therapy is a key part of the effective treatment of the very same disease. Radiation therapy is effective, capable of shrinking and even eliminating tumors. In conjunction with surgery, its use is extremely common for the treatment of breast cancer. Even when radiation is our ally, however, the risks remain. Therapeutic use to treat existing cancers paradoxically leads to the incidence of secondary, radiation-induced neoplasias. One strategy to reduce this secondary risk while still encouraging the use of radiotherapy to its full potential would be the development co-administered therapeutic compounds or strategies designed to preferentially protect healthy cells while leaving cancer cells vulnerable. The development and efficacy testing such agents would require not only extensive in vitro testing, but also a well investigated set of in vivo models to actively recapitulate the complex nature of radiation-induced carcinogenesis. The laboratory mouse Mus musculus is probably the best choice for this endeavor. As a cancer model it possesses a combination of favorable attributes: a well annotated genome, molecular and physiological similarities with man and other mammals, and a small size and high breeding rate for ease of use. This work will focus on the description of m. musculus inbred and F1 hybrid animal models of radiation-induced breast cancers and their associated molecular pathologies.