The development of biological indexes to assess risk of carcinogenicity among workers exposed to dioxins

众所周知，二恶英会导致人类癌症，这一问题引起了公众的极大关注。另一方面，氧化应激现在被广泛认为与致癌性密切相关。了解接触二恶英的工人是否会产生过量的氧化应激，将为预防二恶英致癌提供有用的信息。这项研究旨在开发新的方法或验证新出现的方法来测量氧化应激水平，并建立评估接触二恶英工人致癌风险的方法。为了完成这项研究，我们首先要建立能够有效评估二恶英暴露水平和氧化应激水平的指标，然后验证上述指标是否可能。我们的研究总结如下：1)建立焚烧炉工人二恶英暴露水平的替代指标：在关于…的初步研究的基础上在目标工厂有可能接触到飞灰的更多工种，采访工作历史，特别是关于焚烧炉内、电除尘器内和飞灰固化设备的工作。根据访谈结果，我们计算了每个工人从事工作的时间，其中包括可能接触飞灰的工作。将作业人员分为三组，即长期接触组、短期接触组和对照组。我们还校正了每组部分工人的血液样本，并测量了血液中的二恶英水平。比较这两个指标，我们发现接触飞灰的时间与血液中的二恶英水平有很好的相关性。我们发现，由可能接触飞灰的工作时间构建的指数可以作为二恶英暴露水平的替代指标。2)氧化应激水平的有效评估方法的发展：我们发展了利用电泳法检测氧化反应引起的基因组DNA损伤的方法。然后，我们验证了该方法用于检测与氧化反应引起的基因组DNA损伤相关的尿液物质，证明了该方法是一种定量的、经济有效的方法，可以应用于流行病学研究。3)我们的方法在流行病学研究中的应用：对焚烧炉工人的调查显示，在氧化应激的几个指标中，尿8-OHdG水平与从事可能接触飞灰的工作时间有很好的相关性。我们的结果表明，接触飞灰对工人产生了氧化应激。较少

Dioxin is well known that it causes cancer in human and the issue is of great concern among the public. On the other hand oxidative stress is now widely recognized that it closely relates to carcinogenicity. To know whether excessive oxidative stress is induced among workers exposed to dioxins will be useful information for preventing cancer induced by dioxins. This research is aimed to develop new methods or validate newly appearing methods to measure oxidative stress level and to establish the method for assessing the risk of causing cancers among workers exposed to dioxins. To accomplish this research we first have to develop indexes that could effectively evaluate exposure level of dioxins and oxidative stress level and then to validate whether afore mentioned indexes will possibly of our research is as follows.Summary of our research is as follows.1)Development of indexes that surrogate the exposure level of incinerator workers to dioxins : On the base of the preliminary study abo … More ut job class which has possible exposure to fly ash in the target factory, interview on the job history, especially concerning on the work inside the incinerator, inside the electrical precipitator, and at fly ash solidifying machine. According to the result of the interview, we calculated the duration that each worker engaged in jobs, which includes works that had possible exposure to fly ash. We classified workers into three groups those are long term exposure group, short term exposure group and control group. We also corrected blood samples from a part of workers in each group and measured blood dioxin levels. Comparing these two indexes we found that the duration of exposure to fly ash correlated well with blood dioxin levels. We showed that the index constructed by the duration of engagement in job related to possible exposure to fly ash would be surrogate index to the exposure level of dioxins.2)Development of effective methods to evaluate oxidative stress level : We developed the method to detect genome DNA damage induced by oxidative reaction using electrophoresis. We then validated the ELISA method to detect urinary substance that is related to genome DNA damage induced by oxidative reaction and proved that the method was well quantitative and cost efficient measurement to be applied to epidemiological studies. And also showed that the target substance was stable enough to be good indicator for oxidative stress level of each subject.3)Application of our methods to epidemiological study : Investigation of incinerator workers revealed that among several indexes of oxidative stress, urinary 8-OHdG level had good correlation with the duration engaged in work that has possible exposure to fly ash. Our results suggested that the exposure to fly ash induced oxidative stress to workers. Less