Pharmacological inhibition of DNA repair enzymes differentially modulates telomerase activity and apoptosis in two human leukaemia cell lines

International Journal of Radiation Biology
D DubnerP Gisone

Abstract

To investigate the effect of wortmannin and 3-aminobenzamide (3-AB) on telomerase activity and apoptosis in two human leukaemia cells. MOLT-4 (p53-wild type) and KG1a (p53-null) cells were irradiated with gamma-rays (3 Gy at 1.57 Gy min(-1)) and the effects of wortmannin and 3-AB were evaluated. Telomerase activity was measured by polymerase chain reaction and the expression of human telomerase reverse transcriptase, human telomerase RNA and telomerase-associated protein 1 was assessed by reverse transcriptase-polymerase chain reaction. Apoptosis was evaluated by fluorescence microscopy and flow cytometry. A radiation-induced up-regulation of telomerase activity was observed from 4 h post-irradiation in both cell lines. This up-regulation was abrogated by wortmannin and 3-AB. Telomerase activity was maximal 24 h post-irradiation, coinciding with an accumulation of human telomerase reverse transcriptase mRNA. Apoptosis and G2/M arrest were evident from 4 h post-irradiation in MOLT-4 cells. KG1a cells exhibited a G2/M block at 24 h post-irradiation and apoptosis increased between 24 and 48 h post-irradiation. 3-AB abolished G2/M blockage and enhanced radiation-induced apoptosis in both cell lines, while wortmannin increased apopt...Continue Reading

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Citations

Dec 21, 2006·International Journal of Radiation Biology·Kaisa KurvinenBo Johansson
Jul 8, 2009·Anti-cancer Drugs·Mitra HeraviThierry M Muanza

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