Persistent cell proliferation of terminal end buds precedes radiation-induced rat mammary carcinogenesis

The rat model of radiation-induced carcinogenesis is widely used to estimate breast cancer risk, but it is unknown whether mammary terminal end buds (TEBs), the hypothesized target of chemical carcinogens, are also targets of radiation-induced carcinogenesis.

Female Sprague-Dawley rats were irradiated with X-rays (2 Gy). The morphology, bromodeoxyuridine (BrdU)-labelling index and pyknotic index of mammary ductal termini were investigated from 6 hours to 8 weeks post-irradiation.

The irradiated rats showed a significantly smaller decrease in TEB numbers than the controls 4-8 weeks after irradiation. The BrdU-labelling and pyknotic indices initially decreased and increased, respectively, recovered to control levels by 3 days post-irradiation, and remained significantly higher until 8 weeks and 4 weeks post-irradiation, respectively. One case of ductal hyperplasia was observed at 8 weeks.

Irradiation resulted in a persistent proliferation of TEBs, which may be associated with neoplastic transformation via a temporal differentiation arrest.