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中国毒理学会第七次全国毒理学大会暨第八届湖北科技论坛

作者： Stefan Pfuhler Jie Zhang Procter & Gamble Co Procter & Gamble Technology(Beijing) Co

Historically,studies using laboratory animals such as the in vivo bone marrow MN assay and the in vivo unscheduled DNA synthesis（UDS） assay were used to further evaluate the genotoxic potential of chemicals that are positive in in vitro genotoxicity *** to the 7th Amendment to the Cosmetics Directive of the European Union,since March of 2009,in vivo assays are no longer permitted for genotoxicity testing of cosmetics *** in vivo genotoxicity assays,industry and regulators will have to rely solely on the results of in vitro genotoxicity ***,while showing high sensitivity for detecting carcinogens,these tests have been shown to produce unacceptably high rate of positive results that are not confirmed in in vivo genotoxicity and/or rodent carcinogenicity tests,i.e. "false" positive ***,relying only on results from in vitro genotoxicity assays would severely impact the ability to market potentially safe and beneficial new cosmetic *** address this issue,we developed micronucleus / comet assays that are based on reconstructed human skin *** assays are currently part of a validation exercise sponsored by Cosmetics Europe（formerly COLIPA）.This effort is also supported by the European Center for Validation of Alternative Methods（ECVAM）.Importantly,in April 2014（SCCS/1532/14）,the European Union’s Scientific Committee for Consumer safety（SCCS） highlighted the possibility of in-vitro-only follow-up in case unfavorable results are observed in the standard genotoxicity test battery and emphasizes the utility of 3D skin based genotoxicity assays for such follow-up *** project follows a modular validation approach and is divided into three phases:Phase 1- transferability,optimization,and within-laboratory reproducibility with two model genotoxins;Phase 2- between-laboratory reproducibility with at least five coded chemicals;and Phase 3- increasing the domain of chemicals tested for predictive capacity and fu

关键词： 3D skin comet assays genotoxicity micronucleus assays

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Association Between Polymorphisms of DNA Repair Gene XRCC1 and DNA Damage in Asbestos-Exposed Workers

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Biomedical and Environmental Sciences 2006年第3期19卷 232-238页

作者： XIAO-HONG ZHAO CUANG JIA YONG-QUAN LIU SHAO-WEI LIU LEI YAN YU JIN NIAN LIU Beijing Key Laboratory of Bioactive Substances and Functional Foods Be（jing Union University Beijing 100083 China Department of Occupational and Environmental Health Sciences School of Public Health Peking University Beijing 100083 China Institue of Haidian Health Inspection and Supervision Beijing 100080 China

Objective To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestosexposed workers and 101 control workers in Qingdao City of China and to investigate the possible association between polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. Methods DNA damage levels in peripheral blood lymphocytes were determined by comet assay, and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53 non-asbestosis workers with a similar asbestos exposure history were analyzed by PCR/RFLP. Results The basal comet scores （3.95±2.95） were significantly higher in asbestos-exposed workers than in control workers （0.10±0.28）. After 1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases. After a 4 h repair period, the comet scores were 50.98±19.53 in asbestos-exposed workers and 18.32±12.04 in controls. The residual DNA damage （RD） was significantly greater （P〈0.01） in asbestos-exposed workers （35.62%） than in controls （27.75%）. XRCC1 genetic polymorphism in 104 asbestos-exposed workers was not associated with increased risk of asbestosis. But compared with polymorphisms in the DNA repair gene XRCC1 （polymorphisms in codon 399） and the DNA damage induced by asbestos, the comet scores in asbestosis cases with Gin/Gin, Gln/Arg, and Arg/Arg were 40.26±18.94, 38.03±28.22, and 32.01±11.65, respectively, which were higher than those in non-asbestosis workers with the same genotypes （25.58±11.08, 37.08±14.74, and 29.38±10.15）. There were significant differences in the comet scores between asbestosis cases and non-asbestosis workers with Gin/Gin by Student＇s t-test （P〈0.05 or 0.01）. The comet scores were higher in asbestosis workers with Gin/Gin than in those with Arg/Arg and in non-asbestosis workers exposed to asbestos, but without statistically significant difference. Conclusions Exposure to asbestos may be related to DNA damage or the capacity of cells to repair H2O2-induced DNA damage. DNA re

关键词： Asbestos Asbestosis DNA damage XRCC 1 DNA repair Polymorphisms comet assays

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