Genotoxic activity of azidothymidine (AZT) in in vitro systems.
The genotoxic activity of azidothymidine (AZT) was evaluated in vitro, measuring cytogenetic parameters in two cell systems. In human lymphocytes AZT induced a statistically significant increase in chromosome breakage at 100 micrograms/ml and in micronucleated cells at the highest dose assayed (500 micrograms/ml). Sister-chromatid exchanges (SCE) showed a two-fold increase over control values at 50 micrograms/ml. Lymphocyte cycle kinetics showed an important delay at 500 micrograms/ml. In Chinese hamster ovary (CHO) cells, AZT produced a significant increase in chromosome aberrations and SCE at 1000 and 500 micrograms/ml, respectively. At 2500 micrograms/ml the drug produced a delay in cell cycle progression. These results suggest that AZT is a DNA-damaging agent in both cell systems assayed. Moreover, human lymphocytes seem to be more sensitive to AZT than CHO cells.
González Cid
M
M
Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.
Larripa
I
I
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D006224:Cricetinae; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange; D015215:Zidovudine / Q000633:toxicity*
D009153:Mutagens; D015215:Zidovudine