Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding methyl sulfonate ester.
Cell Death Differ
; 8(8): 817-28, 2001 Aug.
Article
en En
| MEDLINE
| ID: mdl-11526435
The poly(ADP-ribose) polymerase (PARP) is involved in cell recovery from DNA damage, such as methylation of N3-adenine, that activates the base excision repair process. In the present study we demonstrated that MeOSO(2)(CH(2))(2)-lexitropsin (Me-Lex), a methylating agent that almost exclusively produces N3-methyladenine, induced different modalities of cell death in human leukemic cell lines, depending on the presence of PARP inhibitor. Growth inhibition, provoked by the combination of Me-Lex and PARP inhibitor, was associated with a marked down-regulation of c-myc, increased generation of single strand breaks and apoptosis. When used as single agent, at concentrations that saturated cell repair ability, Me-Lex induced mainly cell death by necrosis. Surprisingly, addition of a PARP inhibitor enhanced apoptosis and reduced the early appearance of necrosis. Telomerase activity was completely suppressed in cells exposed to Me-Lex alone, by 24 h after treatment, whereas it did not change when Me-Lex was combined with PARP inhibitor. Thereafter, inhibition of telomerase was observed with both treatments. The results suggest new insights on different modalities of cell death induced by high levels of N3-methyladenine per se, or by the methylated base in the presence of PARP inhibitor.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Apoptosis
/
Metilación de ADN
/
ADN Glicosilasas
/
Proteínas de Unión al ADN
/
Reparación del ADN
/
Inhibidores de Poli(ADP-Ribosa) Polimerasas
/
Necrosis
Límite:
Humans
Idioma:
En
Revista:
Cell Death Differ
Año:
2001
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Reino Unido