Grandi C, D'Ovidio M C, Tomao P
ISPESL - Dipartimento di Medicina del Lavoro, Monteporzio Catone (RM), Italy.
G Ital Med Lav Ergon. 2006 Jan-Mar;28(1):5-13.
The comet test (Single Cell Gel Electrophoresis or SCGE) is an easy to perform, rapid and highly sensitive genotoxicity assay; it requires small amounts of biological substrate and is applicable in vivo and in vitro to a wide variety of cells and tissues. Modified versions of the comet test able to detect oxidative damage or the effects of agents inducing DNA-DNA or DNA-protein crosslinks are available. Similarly to other genotoxicity assays, the comet test is not predictive far individual cancer risk. Limitations and critical features presently linked to comet test applications, with particular regard to the biomonitoring of individuals exposed to genotoxic agents, include: lack of sensitivity with respect to aneugens (agents inducing numerical chromosomal aberrations), possible underestimation of genotoxic potency of agents with mixed action mechanisms, sensitivity depending on the genotoxic agent itself, dependence an biological substrate with regard to the influence of cytotoxicity on the assay results, influence of age, tobacco smoke, alcohol and drug consumption, diet, kinetics of DNA adducts and DNA repair mechanisms. Consequently, a routine use of the comet test in biological monitoring of individuals that are occupationally and environmentally exposed to genotoxic agents is submitted to its validation by multicentric studies on large population samples with different exposure patterns, with a suitable characterisation of the role played by the above mentioned factors. Human studies should also be increasingly focused on the direct cellular targets of exposure to genotoxicants (e.g. epithelial cells of oral cavity and airways).
彗星试验(单细胞凝胶电泳或SCGE)是一种易于操作、快速且高度灵敏的遗传毒性检测方法;它所需生物底物量少,可在体内和体外应用于多种细胞和组织。目前已有能检测氧化损伤或诱导DNA-DNA或DNA-蛋白质交联的试剂作用效果的改良版彗星试验。与其他遗传毒性检测方法类似,彗星试验无法预测个体患癌风险。目前与彗星试验应用相关的局限性和关键特征,尤其是在对接触遗传毒性试剂的个体进行生物监测方面,包括:对非整倍体剂(诱导染色体数目畸变的试剂)缺乏敏感性,对具有混合作用机制的试剂的遗传毒性效力可能低估,敏感性取决于遗传毒性试剂本身,在细胞毒性对检测结果的影响方面依赖生物底物,年龄、烟草烟雾、酒精和药物消费、饮食、DNA加合物动力学以及DNA修复机制的影响。因此,要通过对具有不同暴露模式的大量人群样本进行多中心研究,并对上述因素所起作用进行适当表征,来验证彗星试验在职业和环境中接触遗传毒性试剂个体的生物监测中的常规应用。人体研究也应越来越多地关注接触遗传毒性物质的直接细胞靶点(如口腔和气道上皮细胞)。