Distinct Difference of radiation response between luminal and basal cells in rat mammary glands

Breasts are very susceptible to radiation-induced carcinogenesis, and mammary stem/progenitor cells are potentially important targets of this. The mammary epithelium is maintained as two mostly independent lineages of luminal and basal cells. To reveal their immediate radiation responses, we analyzed the mammary glands of female Sprague-Dawley rats, a radiation carcinogenesis model, using colony formation, flow cytometry (FCM), and immunofluorescence (IF). The results revealed that FCM successfully fractionates rat mammary cells into CD49fhi CD24lo basal, CD49fmed CD24hi luminal progenitor, and CD49flo CD24hi mature luminal populations, resembling human breast, rather than mouse tissues. The colony-forming ability of the basal cells was more radiosensitive than the luminal progenitor cells. FCM and IF showed more efficient cell cycle arrest, yH2AX responses, and apoptosis in the irrad iated luminal progenitor and mature luminal cells, than the basal cells. These results indicate distinct difference of radiation response between luminal and basal cells in rat mammary epithelium, which will provide important insights into the early phase of radiation-induced breast cancer.International Society for Stem Cell Research (ISSCR) 2020 Virtual Annual Meetin