Anderson D
BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK.
Mutat Res. 1999 Jul 16;428(1-2):197-202. doi: 10.1016/s1383-5742(99)00047-2.
"...[Th]e proper study of mankind is man" (Pope, circa 1733/1734). Human monitoring fits this notion and monitoring after exposure to genotoxic agents is now an established discipline. It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and the environment. Responses are often measured in peripheral lymphocytes because these cells can be acquired by a generally socially and ethically acceptable, minimally invasive route. In the early 1960s, chromosome damage in these cells was one of the first endpoints to be used as a biomarker and benzene was one of the first chemicals investigated. Although a causal relationship between chromosome damage and cancer has not been proven, it has been suggested to have some prognostic significance for future cancer onset. With other genetic biomarkers this is as yet not the case, but there are now many biomarkers for different areas of toxicology. Other well-established genetic biomarkers include the detection of hprt mutations, micronuclei and sister chromatid exchanges. However, for interpretation of responses, the issue of confounding factors must be addressed. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure related-problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. Confounding factors affect responses in all cell types. There are endogenous confounding factors such as age, sex, genetic make-up and exogenous confounding factors including lifestyle habits such as smoking, drinking, etc. There are biomarkers of exposure, effect and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects will be considered in relation to workers exposed to vinyl chloride and petroleum emissions. The relationship between the biomarkers and various factors which influence them is complex. Sometimes the variables are not completely independent of one another.
“……人类研究的恰当对象是人”（蒲柏，约1733/1734年）。人体监测符合这一理念，接触遗传毒性剂后的监测如今已成为一门既定学科。在许多情况下，能够识别出 workplace和environment中接触潜在有毒物质的人。通常在外周淋巴细胞中测量反应，因为这些细胞可以通过一般在社会和伦理上可接受的、微创的途径获取。在20世纪60年代早期，这些细胞中的染色体损伤是最早用作生物标志物的终点之一，苯是最早研究的化学物质之一。虽然染色体损伤与癌症之间的因果关系尚未得到证实，但有人认为它对未来癌症发病具有一定的预后意义。对于其他遗传生物标志物，情况并非如此，但现在有许多用于毒理学不同领域的生物标志物。其他已确立的遗传生物标志物包括次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（hprt）突变、微核和姐妹染色单体交换的检测。然而，为了解释反应，必须解决混杂因素的问题。与大多数人体研究一样，对化学损伤的反应往往存在高度的个体间变异性。一些未接触的对照个体表现出与一些接触个体一样高的损伤水平，其中一些个体的损伤水平与许多对照个体一样低。因此，只有群体的平均值才能证实与接触相关的问题；个体层面的数据仍然用途有限。虽然人体淋巴细胞仍然是监测目的最常用的细胞类型，但精子、颊细胞、鼻细胞、上皮细胞和胎盘细胞也被使用。混杂因素会影响所有细胞类型的反应。存在内源性混杂因素，如年龄、性别、基因构成，以及外源性混杂因素，包括吸烟、饮酒等生活方式习惯。有接触、效应和易感性的生物标志物，最后一项可能受人群中存在的基因型和多态性基因影响。从我们自己的研究来看，将结合接触氯乙烯和石油排放的工人来考虑混杂效应。生物标志物与影响它们的各种因素之间的关系很复杂。有时这些变量并非完全相互独立。
