Burns F J, Albert R E, Garte S J
Institute of Environmental Medicine, New York University Medical Center, NY 10016.
Environ Health Perspect. 1989 May;81:67-72. doi: 10.1289/ehp.898167.
Epithelial cell cancers are induced in rat skin by ionizing radiation in a manner that is consistent with the dual action (i.e., two alterations) hypothesis of radiation effects on DNA. This hypothesis states simply that two initial alterations, presumably in the DNA, are necessary to start a normal cell on the pathway to cancer. The initial radiation-induced alteration in the DNA is repairable as indicated by the reduction in tumor incidence with increasing time between dose fractions; the repair halftime is estimated to be 3.0 +/- 1.0 hr. Theoretical predictions of a specific dependence of tumor incidence on linear energy transfer (LET) have been verified experimentally for two specific LET values. However, the theoretical formulation provides no guidance regarding the observed reduction in the carcinogenic action of radiation with age at the time of exposure. Analysis of the tumor DNA for oncogene activation indicated k-ras and c-myc oncogenes were activated in highly anaplastic rat skin cancers, whereas only one of these oncogenes, usually c-myc, was activated in comparatively benign basal cell carcinomas and in squamous cell carcinomas.
电离辐射可在大鼠皮肤中诱发上皮细胞癌，其方式与辐射对DNA影响的双作用（即两种改变）假说一致。该假说简单地指出，可能在DNA中发生的两种初始改变是使正常细胞走上癌变途径所必需的。剂量分割之间时间间隔增加时肿瘤发生率降低，这表明DNA中最初由辐射诱导的改变是可修复的；修复半衰期估计为3.0±1.0小时。对于两个特定的传能线密度（LET）值，肿瘤发生率对LET的特定依赖性的理论预测已通过实验得到验证。然而，该理论公式并未就暴露时辐射致癌作用随年龄的降低给出指导。对肿瘤DNA进行癌基因激活分析表明，在高度间变的大鼠皮肤癌中，k-ras和c-myc癌基因被激活，而在相对良性的基底细胞癌和鳞状细胞癌中，通常只有这些癌基因中的一个，即c-myc被激活。
