Amifostine(WR-2721) selective protection against melphalan genotoxicity

A. Buschini, E. Anceschi, C. Carlo-Stella, E. Regazzi, V. Rizzoli, P. Poli, C. Rossi

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Amifostine (WR-2721) is an aminothiol compound dephosphorylated at the tissue site by alkaline phosphatase to the active metabolite, which is able to inactivate electrophilic substances and scavenge free radicals. Amifostine effects against melphalan-induced DNA strand breaks were studied in normal human white blood cells (WBC) and K562 leukemic cells using the single cell gel electrophoresis (SCGE) or Comet assay, a reported method for measuring DNA damage in individual cells. Prior to treatment (1 h, 37°C) with increasing doses of melphalan, with or without S9, the cells were treated (15 min, 37°C) with a control medium or amifostine (3 mg/ml). Treatment of normal and leukemic cells with melphalan induced a dose-dependent 'comet formation'. Melphalan-induced DNA damage follows a normal distribution in WBC. On the other hand, in K562, a significant proportion of undamaged cells remains even with doses at which mean DNA damage is serious. Pre-treatment with WR-2721 protects WBC, but not K562, against the genotoxic effect of melphalan. Amifostine might even strengthen the action of the antiblastic drug against K562 cells. S9 addition appears to enhance melphalan effectiveness. SCGE appears as a suitable primary screening method for in vitro and in vivo studies on drug-DNA interactions and their modulations by endogenous/exogenous factors.

Original languageEnglish
Pages (from-to)1642-1651
Number of pages10
JournalLeukemia
Volume14
Issue number9
Publication statusPublished - 2000

Fingerprint

Amifostine
Melphalan
Comet Assay
DNA Damage
Leukocytes
K562 Cells
DNA Breaks
Normal Distribution
Drug Interactions
Free Radicals
Alkaline Phosphatase
DNA
Pharmaceutical Preparations

Keywords

  • Antiblastic drugs
  • Comet assay
  • DNA damage
  • Free radical scavenger

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Buschini, A., Anceschi, E., Carlo-Stella, C., Regazzi, E., Rizzoli, V., Poli, P., & Rossi, C. (2000). Amifostine(WR-2721) selective protection against melphalan genotoxicity. Leukemia, 14(9), 1642-1651.

Amifostine(WR-2721) selective protection against melphalan genotoxicity. / Buschini, A.; Anceschi, E.; Carlo-Stella, C.; Regazzi, E.; Rizzoli, V.; Poli, P.; Rossi, C.

In: Leukemia, Vol. 14, No. 9, 2000, p. 1642-1651.

Research output: Contribution to journalArticle

Buschini, A, Anceschi, E, Carlo-Stella, C, Regazzi, E, Rizzoli, V, Poli, P & Rossi, C 2000, 'Amifostine(WR-2721) selective protection against melphalan genotoxicity', Leukemia, vol. 14, no. 9, pp. 1642-1651.
Buschini A, Anceschi E, Carlo-Stella C, Regazzi E, Rizzoli V, Poli P et al. Amifostine(WR-2721) selective protection against melphalan genotoxicity. Leukemia. 2000;14(9):1642-1651.
Buschini, A. ; Anceschi, E. ; Carlo-Stella, C. ; Regazzi, E. ; Rizzoli, V. ; Poli, P. ; Rossi, C. / Amifostine(WR-2721) selective protection against melphalan genotoxicity. In: Leukemia. 2000 ; Vol. 14, No. 9. pp. 1642-1651.
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