DDT对中国仓鼠肺成纤维细胞（V79）遗传毒性的研究
摘要
目的:研究DDT对中国仓鼠肺成纤维细胞V79的遗传毒性。
方法:MTT法测定细胞活性,集落形成试验检测细胞增殖,微核实验测定细胞毒性,染色体畸变分析检测细胞遗传损伤。
结果:与溶剂对照组相比,MTT法结果显示,分别处理4h、8h、12h、24h时6.25μg/ml、12.50μg/ml、25.00μg/ml、50.00μg/ml DDT均可降低V79细胞的活性,与10μg/ml CP的作用类似,有统计学意义(P<0.05),并表现出良好的剂量效应关系和时间效应关系。集落形成实验结果显示,处理4h、8h、12h、24h时12.50μg/ml、25.00μg/ml、50.00μg/ml DDT可抑制V79细胞的增殖,与10μg/ml CP的作用类似具有统计学意义(P<0.05),具有良好的剂量效应和时间效应关系。微核实验结果表明,在无体外活化系统S9参与时,DDT各浓度组对V79细胞微核率结果无统计学意义(P>0.05),表明DDT对V79细胞无明显DNA损伤,没有表现出遗传毒性;添加S9以后,6.25μg/ml、12.50μg/ml、25.00μg/ml、50.00μg/ml DDT均对V79细胞有显著的遗传毒性,此结果有统计学意义(P<0.05),且在6.25μg/ml、50.00μg/ml剂量时呈现剂量效应关系,该关系有统计学意义(P<0.05)。染色体畸变试验结果显示,在不添加S9时,DDT各浓度组对V79细胞染色体畸变效果无统计学意义(P>0.05),视为对细胞染色体没有造成损伤,无明显致畸作用;在有S9系统参与以后,6.25μg/ml、12.50μg/ml、25.00μg/ml、50.00μg/ml DDT均对V79细胞染色体畸变有显著影响,该影响有统计学意义(P<0.05),可造成细胞染色体损伤,且在6.25μg/ml、50.00μg/ml剂量时具有剂量效应关系。
结论:DDT具有与环磷酰胺相似的细胞毒性,能够降低V79细胞的细胞活性,抑制细胞增殖。在体外活化系统S9作用下,DDT可促使V79细胞微核率和染色体畸变发生率的增加,而无体外活化系统S9时此作用不明显。其作用机制可能是在细胞有丝分裂的过程中,造成DNA和染色体的损伤,致使染色体发生突变、断裂,从而表现出潜在的致畸作用。
Objective: To study the genotoxic in Chinese hamster lung fibroblast lines V79 cells by dichloro-diphenyl-trichloroethane.
Mathods: Chinese hamster lung fibroblast lines V79 cells were grown in DMEM medium. MTT assay was employed to investigate the cytoactive of Chinese hamster lung fibroblast lines V79 cells. Colony forming tested the proliferation. Micronucleus assay was used to detect the cytotoxicity and chromosomal aberration was employed to analysis the cell heredity damage.
Results: Compare with the solvent control group, MTT assay result showed that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT in 4h, 8h, 12h, 24h, V79 cells cytoactive would down and appeared dose-effect relationship similaring with the 10μg/ml CP group, has statistically significant (P<0.05). Colony forming test indicated that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT in 4h, 8h, 12h, 24h could restrained V79 cells proliferation and the effective showed with dose-effect and time-effect relationship has statistically significant (P<0.05). Micronucleus assay result showed that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT without S9 could not produce cytotoxicity hasn’t statistically significant (P>0.05). But add S9 could promote DDT produce cytotoxicity and appeared dose-effect relationship in 6.25μg/ml, 50.00μg/ml has statistically significant (P<0.05). Chromosomal aberration outcome appeared that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT without S9 could not promote chromosomal aberration form hasn’t statistically significant (P>0.05). But add S9 could raise chromosomal aberration form and appeared dose-effect relationship in 6.25μg/ml, 50.00μg/ml has statistically significant (P<0.05).
Conclusions: DDT possess cytotoxicity, reduce V79 cells' cytoactive and restrain proliferation. In the effect of invitro activation system S9, DDT can promote V79 cells micronucleus and chromosomal aberration incidence rate. The mechanism of action possibly damage chromosome in the process of cell caryomitotic resulting in the chromosome produce idiovariation and fragmentation thus display carcinogenesis and teratogenicity.
方法:MTT法测定细胞活性,集落形成试验检测细胞增殖,微核实验测定细胞毒性,染色体畸变分析检测细胞遗传损伤。
结果:与溶剂对照组相比,MTT法结果显示,分别处理4h、8h、12h、24h时6.25μg/ml、12.50μg/ml、25.00μg/ml、50.00μg/ml DDT均可降低V79细胞的活性,与10μg/ml CP的作用类似,有统计学意义(P<0.05),并表现出良好的剂量效应关系和时间效应关系。集落形成实验结果显示,处理4h、8h、12h、24h时12.50μg/ml、25.00μg/ml、50.00μg/ml DDT可抑制V79细胞的增殖,与10μg/ml CP的作用类似具有统计学意义(P<0.05),具有良好的剂量效应和时间效应关系。微核实验结果表明,在无体外活化系统S9参与时,DDT各浓度组对V79细胞微核率结果无统计学意义(P>0.05),表明DDT对V79细胞无明显DNA损伤,没有表现出遗传毒性;添加S9以后,6.25μg/ml、12.50μg/ml、25.00μg/ml、50.00μg/ml DDT均对V79细胞有显著的遗传毒性,此结果有统计学意义(P<0.05),且在6.25μg/ml、50.00μg/ml剂量时呈现剂量效应关系,该关系有统计学意义(P<0.05)。染色体畸变试验结果显示,在不添加S9时,DDT各浓度组对V79细胞染色体畸变效果无统计学意义(P>0.05),视为对细胞染色体没有造成损伤,无明显致畸作用;在有S9系统参与以后,6.25μg/ml、12.50μg/ml、25.00μg/ml、50.00μg/ml DDT均对V79细胞染色体畸变有显著影响,该影响有统计学意义(P<0.05),可造成细胞染色体损伤,且在6.25μg/ml、50.00μg/ml剂量时具有剂量效应关系。
结论:DDT具有与环磷酰胺相似的细胞毒性,能够降低V79细胞的细胞活性,抑制细胞增殖。在体外活化系统S9作用下,DDT可促使V79细胞微核率和染色体畸变发生率的增加,而无体外活化系统S9时此作用不明显。其作用机制可能是在细胞有丝分裂的过程中,造成DNA和染色体的损伤,致使染色体发生突变、断裂,从而表现出潜在的致畸作用。
Objective: To study the genotoxic in Chinese hamster lung fibroblast lines V79 cells by dichloro-diphenyl-trichloroethane.
Mathods: Chinese hamster lung fibroblast lines V79 cells were grown in DMEM medium. MTT assay was employed to investigate the cytoactive of Chinese hamster lung fibroblast lines V79 cells. Colony forming tested the proliferation. Micronucleus assay was used to detect the cytotoxicity and chromosomal aberration was employed to analysis the cell heredity damage.
Results: Compare with the solvent control group, MTT assay result showed that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT in 4h, 8h, 12h, 24h, V79 cells cytoactive would down and appeared dose-effect relationship similaring with the 10μg/ml CP group, has statistically significant (P<0.05). Colony forming test indicated that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT in 4h, 8h, 12h, 24h could restrained V79 cells proliferation and the effective showed with dose-effect and time-effect relationship has statistically significant (P<0.05). Micronucleus assay result showed that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT without S9 could not produce cytotoxicity hasn’t statistically significant (P>0.05). But add S9 could promote DDT produce cytotoxicity and appeared dose-effect relationship in 6.25μg/ml, 50.00μg/ml has statistically significant (P<0.05). Chromosomal aberration outcome appeared that given 6.25μg/ml, 12.50μg/ml, 25.00μg/ml, 50.00μg/ml DDT without S9 could not promote chromosomal aberration form hasn’t statistically significant (P>0.05). But add S9 could raise chromosomal aberration form and appeared dose-effect relationship in 6.25μg/ml, 50.00μg/ml has statistically significant (P<0.05).
Conclusions: DDT possess cytotoxicity, reduce V79 cells' cytoactive and restrain proliferation. In the effect of invitro activation system S9, DDT can promote V79 cells micronucleus and chromosomal aberration incidence rate. The mechanism of action possibly damage chromosome in the process of cell caryomitotic resulting in the chromosome produce idiovariation and fragmentation thus display carcinogenesis and teratogenicity.
引文
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[2]联合国环境规划署和世界卫生组织合编.环境卫生基准(9)DDT及其衍生物[M].北京:中国环境科学出版社,1987:1-15.
[3] Annette P H, Philippe G, Torben J. et a1. 0rganochlorine exposure and risk of breast cancer. Lancet. 1998, 52: l8l6-l820.
[4] Laden F, Hankinson S E, Wolf M S, et al. Plasma organochlorine levels and the risk of breast cancer: an extended follow-up in the Nurses Health Study. Int. J Cancer,200l,9l(4):568-574.
[5] Ardies CM, et al. Xenoestrogens significantly enhance risk of. breast cancer during growth and adolescence. J Med Hypotheses.1998, 50(6):457-464.
[6]刘明和.有机氯在我国的污染现状及监控对策[J].内蒙古环境保护,2003,15(1):35-38.
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