Abstract：
Radioresistant cancer cells are risk factors for recurrence and are occasionally detected in recurrent tumors after radiotherapy. Intratumor heterogeneity is believed to be a potential cause of treatment resistance. Heterogeneity in DNA content has also been reported in human colorectal cancer; however, little is known about how such heterogeneity changes with radiotherapy or how it affects cancer radioresistance. In the present study, we established radioresistant clone SW480RR cells after fractionated X-ray irradiation of human colorectal cancer-derived SW480.hu cells, which are composed of two cell populations with different chromosome numbers, and examined how cellular radioresistance changed with fractionated radiotherapy. Compared with the parental cell population, which mostly comprised cells with higher ploidy, the radioresistant clones showed lower ploidy and less initial DNA damage. The lower ploidy cells in the parental cell population were identified as having radioresistance prior to irradiation; thus, SW480RR cells were considered intrinsically radioresistant cells selected from the parental population through fractionated irradiation. This study presents a practical example of the emergence of radioresistant cells from a cell population with ploidy heterogeneity after irradiation. The most likely mechanism is the selection of an intrinsically radioresistant population after fractionated X-ray irradiation, with a background in which lower ploidy cells exhibit lower initial DNA damage.
摘要：
耐辐射癌细胞是复发的危险因素，偶尔在放疗后的复发肿瘤中发现。瘤内异质性被认为是治疗抗性的潜在原因。DNA含量的异质性在人类结肠直肠癌中也有报道；然而，关于这种异质性如何随着放射治疗而改变或如何影响癌症的放射抗性，人们知之甚少。在本研究中,我们在对人大肠癌来源的SW480进行X射线分割照射后，建立了耐放射克隆SW480RR细胞。hu细胞，它们由两个不同染色体数目的细胞群组成，并检查了细胞放射抗性如何随分割放射治疗而变化。与亲本细胞群体相比，主要由具有更高倍性的细胞组成，抗辐射克隆显示出较低的倍性和较少的初始DNA损伤。亲本细胞群中的低倍性细胞在辐照前被鉴定为具有抗辐射性；因此，SW480RR细胞被认为是通过分次照射从亲本群体中选择的固有放射抗性细胞。这项研究提供了一个实际例子，说明辐射后具有倍性异质性的细胞群中出现了耐辐射细胞。最可能的机制是在分割X射线照射后选择固有的耐辐射种群，具有较低倍性细胞表现出较低的初始DNA损伤的背景。
