[Analysis of loss of heterozygosity induced by vinblastine at tk locus in human lymphoblastoid cell line TK6].
摘要
OBJECTIVE: To establish TK gene mutation assay using human lymphoblastoid cell line TK6 and to study the genotoxic mechanism of Vinblastine (VBL). METHODS: TK6 cells were treated with Vinblastine at different concentrations (0.625 ng/mL, 1.250 ng/mL, 2.500 ng/mL and 5.000 ng/mL)for 24 h and TK gene mutation assay were experimented. Relative survival (RS%), relative suspension growth (RSG%), mutation frequency at tk locus and percentages of slow growth mutant (SC%) were detected and loss of heterozygosity (LOH) of mutants were analyzed. RESULTS: A decreased RS% and RSG% and an increased mutation frequency at tk locus were observed in a dose-dependent manner when the TK6 cells were treated with 0.625, 1.250, 2.500 and 5.000 ng/mL of Vinblastine respectively for 24 h. The result demenstrated that about 96.4% of Vinblastine-induced mutants were LOH. Among them, 39.3% were hemi-LOH and 57.1% were homo-LOH respectively. CONCLUSION: TK6 cell line can be used to detect the genotoxicity of Vinblastine and LOH was the major mutation events in Vinblastine-induced mutants.