Fanconi anemia (FA) and crosslinker sensitivity: Re-appraising the origins of FA definition.
The commonly accepted definition of Fanconi anemia (FA) relying on DNA repair deficiency is submitted to a critical review starting from the early reports pointing to mitomycin C bioactivation and to the toxicity mechanisms of diepoxybutane and a group of nitrogen mustards causing DNA crosslinks in FA cells. A critical analysis of the literature prompts revisiting the FA phenotype and crosslinker sensitivity in terms of an oxidative stress (OS) background, redox-related anomalies of FA (FANC) proteins, and mitochondrial dysfunction. This re-appraisal of FA basic defect might lead to innovative approaches both in elucidating FA phenotypes and in clinical management.
Istituto Nazionale Tumori Fondazione G. Pascale-Cancer Research Center at Mercogliano (CROM), Mercogliano (AV), Italy.
Giovanni
G
Pagano
Department of Chemical Sciences, University of Naples "Federico II,", Naples, Italy.
Marco
M
d'Ischia
University of Valencia-INCLIVA, CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Valencia, Spain.
Federico V
FV
Pallardó
D000818:Animals; D043171:Chromosomal Instability; D003432:Cross-Linking Reagents; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D018384:Oxidative Stress
D003432:Cross-Linking Reagents
FANC proteins; Fanconi anemia; bioactivation; crosslinkers; diepoxybutane; glutathione; melphalan; mitomycin C; oxidative stress