Pharmacological inhibition of DNA repair enzymes differentially modulates telomerase activity and apoptosis in two human leukaemia cell lines.
Int J Radiat Biol
; 80(8): 593-605, 2004 Aug.
Article
en En
| MEDLINE
| ID: mdl-15370971
ABSTRACT
PURPOSE:
To investigate the effect of wortmannin and 3-aminobenzamide (3-AB) on telomerase activity and apoptosis in two human leukaemia cells. MATERIALS ANDMETHODS:
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.RESULTS:
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 apoptosis only in MOLT-4 cells.CONCLUSIONS:
3-AB inhibits the radiation-associated telomerase activity increase and enhances apoptosis in MOLT-4 and KG1a cells. Wortmannin, which also inhibits the radiation-associated telomerase activity increase in both cell lines, does not modify radiation-induced apoptosis in KG1a cells. DNA repair enzymes might be selective targets for enhancing radiosensitivity in certain tumour cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzamidas
/
Apoptosis
/
Telomerasa
/
Reparación del ADN
/
Inhibidores Enzimáticos
/
Androstadienos
Límite:
Humans
Idioma:
En
Revista:
Int J Radiat Biol
Asunto de la revista:
RADIOLOGIA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Argentina