Harvey J S, Parry J M
Centre for Molecular Genetics and Toxicology, School of Biological Sciences, University of Wales, Swansea, UK.
Mutat Res. 1998 Mar 13;399(1):31-42. doi: 10.1016/s0027-5107(97)00264-9.
32P-postlabelling was used for the detailed analysis of 4-nitroquinoline 1-oxide (4-NQO) induced DNA adduct formation, removal and persistence in the marine shellfish Mytilus spp. The results had a number of important implications concerning the use of such DNA adducts as dosimeters of environmental genotoxin exposures. Our studies indicated that the maintenance of the Mytilus specimens under controlled laboratory conditions can result in the induction of 'stress-related adducts' seemingly related to the nature of the experimental set-up. The studies also indicated that the absorption and activation of genotoxins in this species appear to affect the rate of adduct formation, and that the maximum levels of adducts may not necessarily be induced immediately after the cessation of a genotoxin exposure. In addition, Mytilus specimens were shown to possess a significant capacity to remove these genotoxin-induced DNA adducts. The removal of these adducts appeared to be biphasic in nature, with the rapid removal of a large proportion of adducts occurring within 48 h of the cessation of the exposure, followed by a slow rate of adduct removal over the remaining period of the studies. Despite the relatively efficient removal of the majority of these genotoxin-induced DNA adducts, a proportion remained up to 56 days after the initial exposure. The persistence of these genotoxin-DNA adducts, combined with the information on the rates of adduct removal, indicated that under well-defined conditions, such adducts could serve as suitable biomarkers of environmental contamination.
采用³²P后标记法详细分析了4-硝基喹啉1-氧化物(4-NQO)诱导海洋贝类紫贻贝属(Mytilus spp.)体内DNA加合物的形成、去除及持久性。这些结果对于将此类DNA加合物用作环境基因毒素暴露剂量计具有诸多重要意义。我们的研究表明,在实验室控制条件下饲养紫贻贝标本可能会诱导产生与实验设置性质相关的“应激相关加合物”。研究还表明,该物种对基因毒素的吸收和活化似乎会影响加合物的形成速率,而且加合物的最高水平不一定在基因毒素暴露停止后立即诱导产生。此外,研究显示紫贻贝标本具有显著的去除这些基因毒素诱导的DNA加合物的能力。这些加合物的去除在性质上似乎呈双相性,在暴露停止后的48小时内,大部分加合物迅速去除,随后在研究的剩余时间内加合物去除速率缓慢。尽管大部分这些基因毒素诱导的DNA加合物得到了相对有效的去除,但仍有一部分在初次暴露后长达56天仍存在。这些基因毒素-DNA加合物的持久性,结合加合物去除速率的信息,表明在明确界定的条件下,此类加合物可作为环境污染的合适生物标志物。