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[Loss of heterozygosity induced by cyclophosphamide at tk locus in human lymphoblastoid cell line TK6]
Li Zhan1, Li-shi Zhang, Li Wang
1National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective:
Human lymphoblastoid cell line TK6 was used to investigate TK gene mutation frequency and the loss of heterozygosity (LOH) induced by cyclophosphamide (CP).
Methods:
Relative survival, mutation frequency at tk locus induced by CP (+S9) after 4 h treatment were detected. DNA isolated from mutants in the control culture and CP treatment group was analyzed for LOH.
Results:
Exposure to CP for 4 h decreased relative survival, induced TK gene mutation in a dose-dependent manner. Doubling time of normally and slowly growing mutants was (14.6 +/- 1.74) h and (35.8 +/- 3.78) h respectively. The percentage of hemizygous LOH in CP-induced mutants (50%) was 2.4 times than that of the control (20.7%).
Conclusion:
Great damage to TK gene is the main cause of mutation induced by CPin TK6 cells.
