Tawn E Janet, Whitehouse Caroline A, Winther Jeanette F, Curwen Gillian B, Rees Gwen S, Stovall Marilyn, Olsen Jørgen H, Guldberg Per, Rechnitzer Catherine, Schrøder Henrik, Boice John D
Westlakes Research Institute, Moor Row, Cumbria CA24 3JY, UK.
Mutat Res. 2005 Jun 6;583(2):198-206. doi: 10.1016/j.mrgentox.2005.03.007.
Suggestions that the induction of genomic instability could play a role in radiation-induced carcinogenesis and heritable disease prompted the investigation of chromosome instability in relation to radiotherapy for childhood cancer. Chromosome analysis of peripheral blood lymphocytes at their first in vitro division was undertaken on 25 adult survivors of childhood cancer treated with radiation, 26 partners who acted as the non-irradiated control group and 43 offspring. A statistically significant increase in the frequency of dicentrics in the cancer survivor group compared with the partner control group was attributed to the residual effect of past radiation therapy. However, chromatid aberrations plus chromosome gaps, the aberrations most associated with persistent instability, were not increased. Therefore, there was no evidence that irradiation of the bone marrow had resulted in instability being transmitted to descendant cells. Frequencies of all aberration categories were significantly lower in the offspring group, compared to the partner group, apart from dicentrics for which the decrease did not reach statistical significance. The lower frequencies in the offspring provide no indication of transmissible instability being passed through the germline to the somatic cells of the offspring. Thus, in this study, genomic instability was not associated with radiotherapy in those who had received such treatment, nor was it found to be a transgenerational radiation effect.
基因组不稳定的诱导可能在辐射致癌和遗传性疾病中起作用，这一观点促使人们对儿童癌症放疗相关的染色体不稳定进行研究。对25名接受过放疗的儿童癌症成年幸存者、26名作为未受辐射对照组的配偶以及43名后代的外周血淋巴细胞首次体外分裂时进行了染色体分析。与配偶对照组相比，癌症幸存者组中双着丝粒频率有统计学意义的增加，这归因于过去放疗的残留效应。然而，与持续不稳定最相关的染色单体畸变加染色体间隙并未增加。因此，没有证据表明骨髓照射导致不稳定传递给后代细胞。与配偶组相比，除双着丝粒外，后代组中所有畸变类别的频率均显著较低，而双着丝粒频率的降低未达到统计学意义。后代中较低的频率并未表明可传递的不稳定通过种系传递给后代的体细胞。因此，在本研究中，接受过放疗的人群中基因组不稳定与放疗无关，也未发现其为跨代辐射效应。
