Oxidative stress in Fanconi anaemia: From cells and molecules towards prospects in clinical management

Giovanni Pagano, Annarita Aiello Talamanca, Giuseppe Castello, Federico V. Pallardó, Adriana Zatterale, Paolo Degan

Research output: Contribution to journalArticle

Abstract

Fanconi anaemia (FA) is a genetic disease featuring bone marrow failure, proneness to malignancies, and chromosomal instability. A line of studies has related FA to oxidative stress (OS). This review attempts to evaluate the evidence for FA-associated redox abnormalities in the literature from 1981 to 2010. Among 2170 journal articles on FA evaluated, 162 related FA with OS. Early studies reported excess oxygen toxicity in FA cells that accumulated oxidative DNA damage. Prooxidant states were found in white blood cells and body fluids from FA patients as excess luminol-dependent chemiluminescence, 8-hydroxy-deoxyguanosine, reduced glutathione/ oxidized glutathione imbalance, and tumour necrosis factor-α. Some FA gene products involved in redox homeostasis can be summarized as follows: (a) FANCA , FANCC , and FANCG interact with cytochrome P450-related activities and/or respond to oxidative damage; (b) FANCD2 in OS response interacts with forkhead box O3 and ataxia telangiectasia mutated protein; (c) FANCG is found in mitochondria and interacts with PRDX3, and FA-G cells display distorted mitochondria and decreased peroxidase activity; (d) FANCJ (BACH1/BRIP1) is a repressor of haeme oxygenase-1 gene and senses oxidative base damage; (e) antioxidants, such as tempol and resveratrol decrease cancer incidence and haematopoietic defects in Fancd2-/- mice. The overall evidence for FA-associated OS may suggest designing chemoprevention studies aimed at delaying the onset of OS-related clinical complications.

Original languageEnglish
Pages (from-to)11-21
Number of pages11
JournalBiological Chemistry
Volume393
Issue number1-2
DOIs
Publication statusPublished - Jan 2012

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Keywords

  • Bone marrow failure
  • Cancer-prone diseases
  • Chemoprevention
  • Chromosomal instability
  • DNA damage
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology

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