Department of Radiation Effects Research, National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Radiat Res. 2020 Jul 8;194(1):22-37. doi: 10.1667/RR15566.1.
Breast tissue is 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 elucidate their immediate radiation responses, we analyzed the mammary glands of female Sprague-Dawley rats, a radiation carcinogenesis model, using colony formation, flow cytometry and immunofluorescence. The results revealed that flow cytometry 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. Flow cytometry and immunofluorescence showed more efficient cell cycle arrest, γ-H2AX responses, and apoptosis in the irradiated luminal progenitor cells, than in the basal cells. These results provide important insights into the early phase of radiation-induced breast cancer.
乳腺组织对辐射诱导的癌变非常敏感,乳腺干细胞/祖细胞可能是这种作用的重要靶点。乳腺上皮组织维持着两个主要的、独立的谱系,即腔细胞和基底细胞。为了阐明它们的即时辐射反应,我们使用集落形成、流式细胞术和免疫荧光技术分析了雌性 Sprague-Dawley 大鼠(一种辐射致癌模型)的乳腺。结果表明,流式细胞术成功地将大鼠乳腺细胞分为 CD49fhi CD24lo 基底细胞、CD49fmed CD24hi 腔前体细胞和 CD49flo CD24hi 成熟腔细胞群体,类似于人类乳腺,而不是小鼠组织。基底细胞的集落形成能力比腔前体细胞更具辐射敏感性。流式细胞术和免疫荧光显示,与基底细胞相比,辐射诱导的腔前体细胞中细胞周期阻滞、γ-H2AX 反应和凋亡更为有效。这些结果为辐射诱导乳腺癌的早期阶段提供了重要的见解。