6533b7ddfe1ef96bd1274ae2

RESEARCH PRODUCT

Gender- and age-related distinctions for the in vivo prooxidant state in Fanconi anaemia patients.

Gerardo BeneduceMarco D'ischiaAnna SavianoFrank J. KellyAdriana ZatteralePaola ManiniAna LloretGiovanni PaganoBruno NobiliFederico V. PallardóMichel WarnauElena De NicolaSema AnakChristina DunsterPaolo DeganEbru E. AkisikRita CalzoneEmilia Vuttariello

subject

MaleCancer Researchmedicine.medical_treatmentTransplantsUrineAscorbic Acidmedicine.disease_causechemistry.chemical_compoundLeukocytesChromosomes HumanVitamin EChildRespiratory BurstGlutathione DisulfideAge FactorsChromosome BreakageGeneral MedicinePyruvaldehydeGlutathioneBiochemistry8-Hydroxy-2'-DeoxyguanosineChild PreschoolFemaleOxidation-ReductionAdultmedicine.medical_specialtyHeterozygoteAdolescentUrinary systemBiologySex FactorsInternal medicinemedicineHumansVitamin CVitamin EDeoxyguanosineInfantGlutathioneDNAAscorbic acidUric AcidOxidative StressEndocrinologyFanconi AnemiachemistryCase-Control StudiesUric acidReactive Oxygen SpeciesOxidative stress

description

Abstract Some selected oxidative stress parameters were measured in 56 Fanconi anaemia (FA) patients (42 untransplanted and 14 transplanted), 54 FA heterozygotes (parents) and 173 controls. Untransplanted FA patients showed a highly significant increase in leukocyte 8-hydroxy-2’-deoxyguanosine (8-OHdG) (p = 0.00003) and a borderline increase (p = 0.076) in urinary levels of 8-OHdG vs. child controls. These increases were more pronounced in female FA patients (p = 0.00005 for leukocyte 8-OHdG, and p = 0.021 for urinary 8-OHdG). Female FA patients also displayed a highly significant excess of spontaneous chromosomal breaks vs. male patients (p = 0.00026), in the same female:male ratio (≅ 1.4) as detected both for leukocyte and for urine 8-OHdG levels. Plasma methylglyoxal (MGlx) levels were increased in untransplanted FA patients vs. child controls (p = 0.032). The increases in leukocyte and urinary 8-OHdG, and in MGlx levels were detected in young FA patients (≤15 yrs), whereas patients aged 16 to 29 yrs failed to display any differences vs. controls in the same age group. A significant increase in oxidised:reduced glutathione (GSSG:GSH) ratio was observed (p = 0.046) in the FA patients aged ≤15 yrs, whereas those aged 16 to 29 yrs, both untransplanted and transplanted, displayed a decrease (p = 0.06) in the GSSG:GSH ratio vs. the controls of the respective age groups. No significant changes were detected in plasma levels of Vitamin C, Vitamin E, or uric acid. Transplanted FA patients showed lesser alterations in leukocyte 8-OHdG and in GSSG:GSH ratio vs. untransplanted patients. The parents of FA patients displayed a significant increase in plasma MGlx levels (p = 0.0014) vs. adult controls. The results suggest a gender- and age-related modulation of oxidative stress in FA patients. The observed increase in urinary 8-OHdG in untransplanted FA patients suggests a proficient removal of oxidised DNA bases. Key words: Fanconi anaemia; 8-hydroxy-2’-deoxyguanosine; methylglyoxal; glutathione; chromosomal instability

yearjournalcountryeditionlanguage
2004-01-01Carcinogenesis
10.1093/carcin/bgh194https://pubmed.ncbi.nlm.nih.gov/15192013