Debio 0507 primarily forms diaminocyclohexane-Pt-d(GpG) and -d(ApG) DNA adducts in HCT116 cells.
Cancer Chemother Pharmacol
; 69(3): 665-77, 2012 Mar.
Article
en En
| MEDLINE
| ID: mdl-21968950
PURPOSE: To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultraperformance liquid chromatography mass spectrometry (UPLC-MS/MS). METHODS: HCT116 cells were treated with IC(50) doses of Debio 0507 or oxaliplatin for 3 days. Total cellular Pt-DNA adducts were determined by ICP-MS. The DNA was digested, and the major Pt-DNA adducts formed by both drugs were characterized by UPLC/MS/MS essentially as described previously for cisplatin (Baskerville-Abraham et al. in Chem Res Toxicol 22:905-912, 2009). RESULTS: The Pt level/deoxynucleotide was 7.4/10(4) for DNA from Debio 0507-treated cells and 5.5/10(4) for oxaliplatin-treated cells following a 3-day treatment at the IC(50) for each drug. UPLC-MS/MS in the positive ion mode confirmed the major Pt-DNA adducts formed by both drugs were dach-Pt-d(GpG) (904.2 m/z â 610 m/z and 904.2 m/z â 459 m/z) and dach-Pt-d(ApG) (888.2 m/z â 594 m/z and 888.2 m/z â 459 m/z). CONCLUSIONS: These data show that the major DNA adducts formed by Debio 0507 are the dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts and at equitoxic doses Debio 0507 and oxaliplatin form similar levels of dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts. This suggests that the action mechanisms of Debio 0507 and oxaliplatin are similar at a cellular level.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organoplatinos
/
Fosfatos de Dinucleósidos
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Aductos de ADN
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Nucleótidos de Desoxiadenina
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Desoxiguanosina
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Alemania