title: Gender- and age-related distinctions for the in vivo prooxidant state in Fanconi anaemia patients.
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 versus 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 versus male patients (P = 0.00026), in the same female:male ratio ( approximately 1.4) as detected for both leukocyte and urine 8-OHdG levels. Plasma methylglyoxal (MGlx) levels were increased in untransplanted FA patients versus child controls (P = 0.032). The increases in leukocyte and urinary 8-OHdG and in MGlx levels were detected in young FA patients (< or =15 years), whereas patients aged 16-29 years failed to display any differences versus controls in the same age group. A significant increase in oxidized:reduced glutathione (GSSG:GSH) ratio was observed (P = 0.046) in the FA patients aged < or =15 years, whereas those aged 16-29 years, both untransplanted and transplanted, displayed a decrease (P = 0.06) in the GSSG:GSH ratio versus 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 versus untransplanted patients. The parents of FA patients displayed a significant increase in plasma MGlx levels (P = 0.0014) versus 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 oxidized DNA bases.
authors.affiliation: Italian National Cancer Institute, G. Pascale Foundation, Via M.Semmola 12, I-80131 Naples, Italy. gbpagano@tin.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pagano
authors.forename: Paolo
authors.initials: P
authors.lastname: Degan
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kelly
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
authors.forename: Adriana
authors.initials: A
authors.lastname: Zatterale
authors.forename: S Sema
authors.initials: SS
authors.lastname: Anak
authors.forename: Ebru E
authors.initials: EE
authors.lastname: Akisik
authors.forename: Gerardo
authors.initials: G
authors.lastname: Beneduce
authors.forename: Rita
authors.initials: R
authors.lastname: Calzone
authors.forename: Elena
authors.initials: E
authors.lastname: De Nicola
authors.forename: Christina
authors.initials: C
authors.lastname: Dunster
authors.forename: Ana
authors.initials: A
authors.lastname: Lloret
authors.forename: Paola
authors.initials: P
authors.lastname: Manini
authors.forename: Bruno
authors.initials: B
authors.lastname: Nobili
authors.forename: Anna
authors.initials: A
authors.lastname: Saviano
authors.forename: Emilia
authors.initials: E
authors.lastname: Vuttariello
authors.forename: Michel
authors.initials: M
authors.lastname: Warnau
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001205:Ascorbic Acid / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002877:Chromosomes, Human; D004247:DNA / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine*; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011765:Pyruvaldehyde / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000502:physiology; D012737:Sex Factors; D019737:Transplants; D014527:Uric Acid / Q000097:blood; D014810:Vitamin E / Q000097:blood
chemical_list: D017382:Reactive Oxygen Species; D014810:Vitamin E; D014527:Uric Acid; D011765:Pyruvaldehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D005978:Glutathione; D001205:Ascorbic Acid; D019803:Glutathione Disulfide