Robinson D R, Goodall K, Albertini R J, O'Neill J P, Finette B, Sala-Trepat M, Moustacchi E, Tates A D, Beare D M, Green M H
Department of Mathematics, University of Sussex, Falmer, Brighton, UK.
Mutat Res. 1994 Oct-Dec;313(2-3):227-47. doi: 10.1016/0165-1161(94)90053-1.
In this paper, we have compared mutant frequency data at the hprt locus in circulating T-lymphocytes from four large datasets obtained in the UK (Sussex), the USA (Vermont), France (Paris) and The Netherlands (Leiden). In total, data from > 500 non-exposed individuals ranging in age from newborns (cord blood samples) to > 80 years old have been included in the analysis. Based on raw data provided by the four laboratories, a model is presented for the analysis of mutant frequency estimations for population monitoring. For three of the laboratories, a considerable body of data was provided on replicate estimates of mutant frequency from single blood samples, as well as estimates from repeat blood samples obtained over a period of time from many of the individual subjects. This enabled us to analyse the sources of variation in the estimation of mutant frequency. Although some variation was apparent in the results from the four laboratories, overall the data were in general agreement. Thus, in all laboratories, cellular cloning efficiency of T-cells was generally high (> 30%), although in each laboratory considerable variation between experiments and subjects was seen. Mutant frequency per clonable T-cell was in general found to be inversely related to cloning efficiency. With the exception of a few outliers (which are to be expected), mutant frequencies at this locus were in the same range in each dataset; no effect of subject gender was found, but an overall clear age effect was apparent. When log mutant frequency was analysed vs log (age + 0.5) a consistent trend from birth to old age was seen. In contrast, the effect of the smoking habit did differ between the laboratories, there being an association of smoking with a significant increase in mutant frequency in the Sussex and Leiden datasets, but not in those from the Vermont or Paris datasets. Possible reasons for this are discussed. One of the objectives of population monitoring is an ability to detect the effect of accidental or environmental exposure to mutagens and carcinogens among exposed persons. The large body of data from non-exposed subjects we have analysed in this paper has enabled us to estimate the size of an effect that could be detected, and the number of individuals required to detect a significant effect, taking known sources of variation into account.(ABSTRACT TRUNCATED AT 400 WORDS)
在本文中，我们比较了来自英国（苏塞克斯）、美国（佛蒙特）、法国（巴黎）和荷兰（莱顿）的四个大型数据集中循环T淋巴细胞hprt位点的突变频率数据。分析总共纳入了500多名非暴露个体的数据，年龄范围从新生儿（脐血样本）到80多岁。基于四个实验室提供的原始数据，提出了一个用于分析群体监测中突变频率估计值的模型。对于其中三个实验室，提供了大量关于单个血样中突变频率重复估计的数据，以及许多个体受试者在一段时间内采集的重复血样的估计数据。这使我们能够分析突变频率估计中的变异来源。尽管四个实验室的结果存在一些明显差异，但总体数据基本一致。因此，在所有实验室中，T细胞的细胞克隆效率普遍较高（>30%），不过在每个实验室中，实验和受试者之间存在相当大的差异。每个可克隆T细胞的突变频率通常与克隆效率呈负相关。除了少数异常值（这是可以预料的）外，每个数据集中该位点的突变频率处于相同范围；未发现受试者性别的影响，但明显存在总体年龄效应。当分析对数突变频率与对数（年龄 + 0.5）的关系时，从出生到老年呈现出一致的趋势。相比之下，吸烟习惯的影响在不同实验室之间存在差异，在苏塞克斯和莱顿数据集中，吸烟与突变频率显著增加有关，而在佛蒙特或巴黎数据集中则不然。本文讨论了可能的原因。群体监测的目标之一是能够检测暴露人群中意外或环境接触诱变剂和致癌物的影响。我们在本文中分析的大量未暴露受试者的数据，使我们能够估计在考虑已知变异来源的情况下，可以检测到的效应大小以及检测到显著效应所需的个体数量。（摘要截断于400字）
