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 MeOSO2(CH2)(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.

Tentori, L., Balduzzi, A., Portarena, I., Levati, L., Vernole, P., Gold, B., et al. (2001). Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding methyl sulfonate ester. CELL DEATH AND DIFFERENTIATION, 8(8), 817-828.

Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding methyl sulfonate ester

TENTORI, LUCIO;VERNOLE, PATRIZIA;BONMASSAR, ENZO;GRAZIANI, GRAZIA
2001-01-01

Abstract

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 MeOSO2(CH2)(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.
2001
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Apoptosis; Drug resistance; Methylating agents; Necrosis; Poly(ADP-ribose) polymerase; Telomerase
Tentori, L., Balduzzi, A., Portarena, I., Levati, L., Vernole, P., Gold, B., et al. (2001). Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding methyl sulfonate ester. CELL DEATH AND DIFFERENTIATION, 8(8), 817-828.
Tentori, L; Balduzzi, A; Portarena, I; Levati, L; Vernole, P; Gold, B; Bonmassar, E; Graziani, G
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/52887
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