Wones R, Radack K, Martin V, Mandell K, Pinney S, Buncher R
Department of Medicine, University of Cincinnati School of Medicine, OH 45267-0535, USA.
Mutat Res. 1995 Oct;335(2):171-84. doi: 10.1016/0165-1161(95)90053-5.
The objective of this study was to examine if individuals living near a uranium processing site have greater mutagenic damage, as measured by three mutagenicity assays, compared with subjects unexposed to any nuclear facilities. The design was a cross-sectional exploratory analysis of 112 subjects; 56 volunteer residents were from within a 5-mile radius of the Fernald Uranium Processing site and 56 'control' subjects were from a geographically separate area unexposed to any known uranium emissions. The groups were constrained to be similar in age and sex composition. The main outcome measures were three human somatic gene mutation assays consisting of the HPRT T-lymphocyte cloning assay to measure 6-thioguanine resistant lymphocytes; the glycophorin A assay to detect the loss of expression of the M or N allele; and the micronucleus assay as a marker of chromosomal damage. The results showed no statistically significant or quantitatively important differences between groups for all three mutagenicity assays; only the unselected cloning efficiency was statistically significantly different between groups (0.42 +/- 0.16 for the Fernald versus 0.35 +/- 0.12 for the comparison groups). In both groups, age was significantly related to HPRT mutant frequency, with a 1.25% rate of increase in mutant frequencies for each 1-year gain of age in the Fernald group and a 1.12% rate of increase in mutant frequencies for each 1-year gain of age in the comparison group. For the micronucleus data, females had a greater mean micronucleus frequency than males. In addition, smokers had an increased mean ln (natural logarithm) HPRT mutant frequency (3.06 +/- 0.14 for current smokers compared with a mean of 2.72 +/- 0.05 for non-current (i.e. never plus former) smokers). Our results are consistent with the previously reported association between sex type and micronucleus frequency, the known relationship between age and T-lymphocyte cloning efficiency and age and HPRT mutant frequency, and verify the wide inter-subject variability for the latter. Finally, we conclude that at a population level, the relationships between current cigarette use and HPRT mutant frequency, and sex type and micronucleus frequency, are stronger than is the association between geographic proximity to a uranium processing site and mutagenic abnormalities.
本研究的目的是通过三种致突变性检测方法，检验居住在铀加工场地附近的个体与未接触任何核设施的受试者相比，是否具有更大的诱变损伤。研究设计为对112名受试者进行横断面探索性分析；56名志愿者居民来自弗纳尔德铀加工场地半径5英里范围内，56名“对照”受试者来自地理上独立且未接触任何已知铀排放的区域。两组在年龄和性别构成上受到限制以使其相似。主要结局指标是三种人体体细胞基因突变检测方法，包括用于测量对6-硫鸟嘌呤耐药淋巴细胞的次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）T淋巴细胞克隆检测；用于检测M或N等位基因表达缺失的血型糖蛋白A检测；以及作为染色体损伤标志物的微核检测。结果显示，在所有三种致突变性检测中，两组之间在统计学上无显著差异或在数量上无重要差异；仅未选择的克隆效率在两组之间有统计学显著差异（弗纳尔德组为0.42±0.16，而对照组为0.35±0.12）。在两组中，年龄与HPRT突变频率显著相关，在弗纳尔德组中，年龄每增加1岁，突变频率增加率为1.25%，在对照组中，年龄每增加1岁，突变频率增加率为1.12%。对于微核数据，女性的平均微核频率高于男性。此外，吸烟者的平均自然对数HPRT突变频率增加（当前吸烟者为3.06±0.14，而非当前吸烟者（即从不吸烟加既往吸烟者）的平均值为2.72±0.05）。我们的结果与先前报道的性别类型与微核频率之间的关联、年龄与T淋巴细胞克隆效率以及年龄与HPRT突变频率之间的已知关系一致，并证实了后者在受试者之间存在广泛的变异性。最后，我们得出结论，在人群水平上，当前吸烟与HPRT突变频率之间以及性别类型与微核频率之间的关系，比居住地点与铀加工场地的地理距离和诱变异常之间的关联更强。
