[Analysis of loss of heterozygosity induced by vinblastine at tk locus in human lymphoblastoid cell line TK6].
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.


CONCLUSIONS
TK6 cell line can be used to detect the genotoxicity of Vinblastine and LOH was the major mutation events in Vinblastine-induced mutants.
Wang
Ya-nan
YN
Department of Nutrition and Food Hygiene, West China School of Public Health, Sichuan University, Chengdu 610041, China.
Shuai
Pei-qiang
PQ
Guo
Ya-jie
YJ
Zhang
Li-shi
LS
D002460:Cell Line; D006801:Humans; D019656:Loss of Heterozygosity / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D013937:Thymidine Kinase / Q000235:genetics*; D014747:Vinblastine / Q000633:toxicity*
D009153:Mutagens; D014747:Vinblastine; D013937:Thymidine Kinase