title: Prospects for nutritional interventions in the clinical management of Fanconi anemia.
abstract: The evidence associating Fanconi anemia (FA) phenotype to in-vitro and ex-vivo oxidative stress is reviewed. A cancer-prone genetic disease, FA is characterized by delayed bone marrow failure with a progression to aplastic anemia. It is diagnosed by excess chromosomal instability induced by two clastogens, either diepoxybutane (DEB) or mitomycin C (MMC). Clinical symptoms vary in a broad range including a life-threatening hematological impairment, and an extended set of developmental abnormalities, growth retardation and skin pigmentation. Cancer-proneness in FA results in excess incidence of non-lymphoblastic leukemias, and of some defined solid tumors. The relationships of oxidative stress with FA phenotype rely on a consistent body of evidence that includes: (1) excess formation of DNA oxidative damage (both in vitro and in vivo); (2) cellular protection by hypoxia, low molecular-weight antioxidants, antioxidant enzymes, and thioredoxin overexpression; (3) impaired expression and/or activity of antioxidant enzymes, and (4) the redox-dependent action mechanisms of MMC and DEB. This evidence points to a re-appraisal of FA phenotype, suggesting a causative role for oxidative stress in disease progression towards malignancies and/or bone marrow depletion. A well-established literature reporting epidemiological and experimental data provides the nutritional bases for cancer control. Thus, the present state-of-the-art in the related fields of oxidative stress, nutrition, cancer-proneness and FA phenotype, altogether implies the need to undertake the most appropriate efforts to counteract oxidative stress in the clinical management of FA patients.
authors.affiliation: Istituto Nazionale Tumori, Fondazione G. Pasacle, Naples, Italy. gbpagano@tin.it
authors.forename: G
authors.initials: G
authors.lastname: Pagano
authors.forename: L G
authors.initials: LG
authors.lastname: Korkina
mesh_terms: D000741:Anemia, Aplastic / Q000209:etiology / Q000503:physiopathology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D004852:Epoxy Compounds / Q000494:pharmacology; D005199:Fanconi Anemia / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D009752:Nutritional Status; D018384:Oxidative Stress; D010641:Phenotype
chemical_list: D000903:Antibiotics, Antineoplastic; D004852:Epoxy Compounds; D016685:Mitomycin; C007366:diepoxybutane