Busch D
Department of Environmental and Toxicologic Pathology, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000.
Int J Radiat Oncol Biol Phys. 1994 Nov 15;30(4):997-1002. doi: 10.1016/0360-3016(94)90378-6.
Over 5% of the cancer patient population may be radiation sensitive due to genetics, and the sensitive patients may be greatly overrepresented among patients with cancer therapy complications. These individuals include not only rare ataxia telangiectasia (AT) homozygotes with up to three-fold normal radiation sensitivity, but also far more numerous patients with slight radiosensitivity conjectured to be carriers of AT or to have another inherited mutagen sensitivity. Procedures may eventually be used to reliably determine patient tolerance for radiation and antineoplastic agents before initiation or completion of therapy, to have the therapy approach but not exceed the radiation tolerance of the individual patient's irradiated normal tissue. Such procedures could include study of patient's cultured normal cells (e.g., fibroblasts, marrow cells, or lymphocytes) in much the same way that patients' cultured tumor cells may eventually be widely used in the human tumor stem cell assay to predict which course of radiotherapy or chemotherapy should be most useful for treating a cancer. Studies with the normal cells could include cytotoxicity assays, serially determined accumulated genetic damage over the course of therapy, or Southern blot analysis to identify carriers of DNA repair mutations. Such studies could permit more aggressive radiotherapy of most patients due to the noninclusion of a sensitive subpopulation of patients, with less radiotherapy of the relatively few radiation sensitive patients. The patient's tumor cells should have inherited any radiation (or chemotherapy) sensitivity mutations present in the patient's normal cells, so reducing the radiotherapy dose to compensate for the more radiosensitive patients' sensitivity will not necessarily result in undertreatment of the tumor.
超过5%的癌症患者群体可能由于遗传因素而对辐射敏感，在患有癌症治疗并发症的患者中，敏感患者的比例可能会大大超过正常水平。这些个体不仅包括罕见的共济失调毛细血管扩张症（AT）纯合子，其辐射敏感性高达正常水平的三倍，还包括数量多得多的轻度放射敏感患者，据推测他们是AT的携带者或具有另一种遗传性诱变敏感性。最终可能会采用一些方法，在治疗开始或完成之前可靠地确定患者对辐射和抗肿瘤药物的耐受性，使治疗方案符合但不超过个体患者受照射正常组织的辐射耐受性。这样的方法可能包括研究患者的培养正常细胞（如成纤维细胞、骨髓细胞或淋巴细胞），就像患者的培养肿瘤细胞最终可能会广泛应用于人类肿瘤干细胞检测，以预测哪种放疗或化疗方案对治疗癌症最有效一样。对正常细胞的研究可能包括细胞毒性检测、在治疗过程中连续测定累积的遗传损伤，或进行Southern印迹分析以识别DNA修复突变的携带者。由于不包括敏感患者亚群，此类研究可能会使大多数患者接受更积极的放疗，而对相对较少的辐射敏感患者进行较少的放疗。患者的肿瘤细胞应该继承了患者正常细胞中存在的任何辐射（或化疗）敏感性突变，因此降低放疗剂量以补偿辐射敏感患者的敏感性不一定会导致肿瘤治疗不足。
