title: Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management.
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.
authors.affiliation: Italian Association for Fanconi Anaemia Research, I-80133 Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pagano
authors.forename: Annarita Aiello
authors.initials: AA
authors.lastname: Talamanca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
authors.forename: Adriana
authors.initials: A
authors.lastname: Zatterale
authors.forename: Paolo
authors.initials: P
authors.lastname: Degan
mesh_terms: D000818:Animals; D005199:Fanconi Anemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D006801:Humans; D018384:Oxidative Stress