Albertini R J, Clark L S, Nicklas J A, O'Neill J P, Hui T E, Jostes R
University of Vermont, Genetics Laboratory, Burlington 05401, USA.
Radiat Res. 1997 Nov;148(5 Suppl):S76-86.
Human T lymphocytes can be used to determine the frequency and molecular spectrum of somatic cell gene mutations induced by ionizing radiations both in vivo and in vitro. In vitro exposure of these G0 cells to low-LET 137Cs gamma rays results in the induction of HPRT mutations and a predominant molecular spectrum of DNA deletions and rearrangements, particularly total gene deletions (11-12%). Similar results are found in samples from humans exposed to low-LET radiation from 131I. The doubling dose for mutation induction is calculated to be 0.8 and 1.0 Gy from these exposures performed in vitro and in vivo, respectively. In vitro studies of the effects of high-LET radiation from exposure to 222Rn also showed an induction of HPRT mutations, with a doubling dose of approximately 0.2 Gy. With this radiation, the predominant mutations were small partial deletions, with less than 2% total gene deletions. Studies of humans exposed to high-LET radiation from 239Pu showed an increased HPRT mutant frequency for the group, although no significant dosimetry could be defined. In contrast to the humans exposed to 131I, no increase in the frequency of total gene deletions was found. This is consistent with the results for 222Rn in vitro. The available data show that radiation quality affects both the efficiency of induction and the molecular spectrum of HPRT mutations in human T lymphocytes both in vitro and in vivo. The mutational spectrum may be relatively specific for radiations of different quality and thus allow a more precise measurement of the induction of somatic gene mutations resulting from individual exposures to radiation, and thereby provide more sensitive assessments of health risks.
人类T淋巴细胞可用于确定体内和体外电离辐射诱导的体细胞基因突变的频率和分子谱。将这些G0期细胞在体外暴露于低传能线密度的137Csγ射线会导致次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HPRT)基因突变的诱导,以及DNA缺失和重排的主要分子谱,特别是全基因缺失(11%-12%)。在暴露于131I低传能线密度辐射的人类样本中也发现了类似结果。根据分别在体外和体内进行的这些暴露实验,计算出突变诱导的倍加剂量分别为0.8 Gy和1.0 Gy。对暴露于222Rn高传能线密度辐射影响的体外研究也显示了HPRT基因突变的诱导,倍加剂量约为0.2 Gy。对于这种辐射,主要的突变是小的部分缺失,全基因缺失少于2%。对暴露于239Pu高传能线密度辐射的人类研究表明,该组的HPRT突变频率增加,尽管无法确定显著的剂量测定值。与暴露于131I的人类不同,未发现全基因缺失频率增加。这与体外暴露于222Rn的结果一致。现有数据表明,辐射质量在体外和体内均会影响人类T淋巴细胞中HPRT基因突变的诱导效率和分子谱。突变谱可能对不同质量的辐射具有相对特异性,因此可以更精确地测量个体辐射暴露导致的体细胞基因突变的诱导情况,从而对健康风险提供更敏感的评估。