用tk基因突变试验评价长春新碱和秋水仙碱的遗传毒性

Evaluation of the genotoxicity of vincristine and colchicine using mouse lymphoma tk mutation assay

目的评价有丝分裂抑制剂长春新碱和秋水仙碱的遗传毒性,并比较短期和长期tk基因突变试验的检出灵敏度.方法用长春新碱和秋水仙碱对小鼠淋巴瘤细胞分别进行3h及24h染毒,用微孔板法进行tk基因突变试验,计算相对悬浮生长、接种效率、相对存活率、相对总生长及突变频率等指标,并比较短期和长期处理的结果.结果两种受试物3h处理均未出现明显的阳性反应,而24h连续处理后,两种受试物均能诱导tk基因突变频率增高,诱发突变频率分别为自发突变频率的1.6～4.8倍和2.1～6.2倍,呈阳性结果.结论长春新碱和秋水仙碱在长期处理试验中能诱导tk基因突变,而在短期处理试验中未发现明显诱变性,即长期处理能提高tk基因突变试验的检出灵敏度.

Objective To evaluate the genotoxicity of two mitotic inhibitors vincristine and colchicine, and to compare the detecting sensitivity of tk gene mutation assay with short-and long-term treatment by them.Methods Tk gone mutation assay was performed by microwell method with L5178Y mouse lymphoma cell line after exposing to vincfistine and colchicine for 3h and 24h respectively, and the results of two different treating time were compared. Results The two chemicals didn＇t show positive responses in mouse lymphoma assay （MLA） with 3h treatment, but they could induce tk mutation frequency increase 1.6 to 4.8 and 2.1 to 6.2 times higher to spontaneous MF respectively after continuous treatment for 24h. Conclusion Vincristine and colchicine had mutagenic effect on tk gene with long-term treatment, which indicated that the detecting sensitivity of MLA could be enhanced by long-term treatment.