Kleinerman R A, Littlefield L G, Tarone R E, Sayer A M, Cookfair D L, Wactawski-Wende J, Inskip P D, Block A, Ramesh K H, Boice J D
Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Radiat Res. 1994 Jul;139(1):40-6.
Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow (8 Gy vs 0.7 Gy, respectively). High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received.
宫颈癌和良性妇科疾病（BGD）患者接受局部放疗后出现了白血病病例增多的情况。然而，尽管两组患者接受的活跃骨髓平均剂量相差10倍（分别为8 Gy和0.7 Gy），但两组的风险水平几乎相同，约为两倍。高剂量细胞杀伤被认为是这种明显矛盾现象的一种解释。为了检验多年前暴露后淋巴细胞中观察到的染色体畸变率是否可作为癌症风险的群体标志物，从60名接受BGD治疗的女性（34名接受放疗）中采集了血样，并将细胞遗传学数据与之前96名接受宫颈癌放疗的女性的结果进行了比较。值得注意的是，反映存活干细胞非致死性损伤的稳定畸变率在癌症患者中仅略高。因此，治疗良性疾病的低剂量方案导致的单位剂量畸变率远高于宫颈癌治疗方案。假设放疗后存活的细胞遗传学异常干细胞部分会导致白血病发生过程，那么这些数据与这两个接受放疗人群中总体白血病风险相当的流行病学观察结果是一致的。因此，对于接受局部放疗的患者群体，暴露后很长时间出现的稳定畸变似乎是有效风险的生物标志物，而非所接受辐射剂量的生物标志物。
