Erdal Serap, McCarthy Bridget J, Gurule Natalia, Berwick Marianne, Gonzales Emily, Byrd Johanna, Flores Kristina, Shimek JoAnna, Il'yasova Dora, Ali-Osman Francis, Bigner Darell D, Davis Faith G, Leyba Alexis N, White Kirsten A M
Divisions of Environmental, Occupational Health Science, University of Illinois at Chicago, Chicago, IL, United States.
Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL, United States.
Toxicol Rep. 2018 Jan 9;5:183-188. doi: 10.1016/j.toxrep.2017.12.010. eCollection 2018.
Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in animal models. The mutagen sensitivity assay (MSA) has been used to indirectly show reduced DNA repair capacity upon exposure to ionizing radiation in those with glioma compared to controls. In this study, MSA was used to assess its applicability to a glioma case-control study and to test the hypothesis that subjects with glioma may have lower DNA repair capacity after exposure to selected potential human neurocarcinogens (i.e. acrylamide), compared to controls. Approximately 50 case and 50 control subjects were identified from a clinic-based study that investigated environmental risk factors for glioma, who completed an exposure survey, and had frozen immortalized lymphocytes available. A total of 50 metaphase spreads were read and reported for each participant. The association of case-control status with MSA for acrylamide, i.e. breaks per spread, was examined by multivariable logistic regression models. The mean number of breaks per slide was similar between hospital-based controls and cases. In addition, case-control status or exposure categories were not associated with the number of breaks per spread. Although the MSA has been shown as a useful molecular epidemiology tool for identifying individuals at higher risk for cancer, our data do not support the hypothesis that glioma patients have reduced DNA repair capacity in response to exposure to acrylamide. Further research is needed before the MSA is utilized in large-scale epidemiological investigations of alkylating agents.
除了电离辐射外，很少有胶质瘤的风险因素被确定。烷基化剂丙烯酰胺是一种在职业环境和一般环境中都能找到的化合物，在动物模型中被确定为四十种已知或疑似神经致癌物之一。诱变敏感性测定（MSA）已被用于间接表明，与对照组相比，胶质瘤患者在暴露于电离辐射后DNA修复能力降低。在本研究中，MSA被用于评估其在胶质瘤病例对照研究中的适用性，并检验以下假设：与对照组相比，胶质瘤患者在暴露于选定的潜在人类神经致癌物（即丙烯酰胺）后，其DNA修复能力可能较低。从一项基于临床的研究中确定了约50例病例和50例对照，该研究调查了胶质瘤的环境风险因素，这些受试者完成了暴露调查，并有冷冻的永生化淋巴细胞可用。为每位参与者读取并报告了总共50个中期染色体铺展。通过多变量逻辑回归模型检验病例对照状态与丙烯酰胺MSA（即每个铺展的断裂数）之间的关联。医院对照和病例之间每张玻片的平均断裂数相似。此外，病例对照状态或暴露类别与每个铺展的断裂数无关。尽管MSA已被证明是一种用于识别癌症高危个体的有用分子流行病学工具，但我们的数据并不支持胶质瘤患者在暴露于丙烯酰胺后DNA修复能力降低的假设。在将MSA用于烷基化剂的大规模流行病学调查之前，还需要进一步的研究。
