[Loss of heterozygosity induced by cyclophosphamide at tk locus in human lymphoblastoid cell line TK6].
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%).


CONCLUSIONS
Great damage to TK gene is the main cause of mutation induced by CPin TK6 cells.
Zhan
Li
L
National Chengdu Center for Safety Evaluation of Traditional Chinese Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhang
Li-shi
LS
Wang
Li
L
Zhang
Hao
H
Takayoshi
Suzuki
S
Masamitsu
Honma
H
Wu
De-sheng
DS
D002460:Cell Line; D003520:Cyclophosphamide / Q000633:toxicity*; D006801:Humans; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000166:cytology*; D009154:Mutation; D013937:Thymidine Kinase
D003520:Cyclophosphamide; D013937:Thymidine Kinase