Biochemical grounds for "crosslinker sensitivity": What have we learned from pharmacology?

The literature pointing to mitomycin C bioactivation, and to the toxicity mechanisms of diepoxybutane and a group of nitrogen mustards causing DNA crosslinks in Fanconi Anemia (FA) cells is reviewed. A critical analysis of this 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 phenotype and in prospect developments of patients' clinical management.