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

被引:43
作者
Pagano, G
Degan, P
d'Ischia, M
Kelly, FJ
Pallardó, FV
Zatterale, A
Anak, SS
Akisik, EE
Beneduce, G
Calzone, R
De Nicola, E
Dunster, C
Lloret, A
Manini, P
Nobili, B
Saviano, A
Vuttariello, E
Warnau, M
机构
[1] G Pascale Fdn, Italian Natl Canc Inst, I-80131 Naples, Italy
[2] IST, Italian Natl Canc Inst, Genoa, Italy
[3] Univ Naples Federico II, Dept Organ Chem & Biochem, Naples, Italy
[4] Kings Coll London, Div Life Sci, London W8 7AH, England
[5] Univ Valencia, Dept Physiol, Valencia, Spain
[6] ASL Napoli 1, Elena dAosta Hosp, Dept Genet, Naples, Italy
[7] Istanbul Univ, Dept Paediat Haematol, Istanbul, Turkey
[8] Univ Naples 2, Dept Paediat, Naples, Italy
[9] Cardarelli Hosp, Dept Paediat, Naples, Italy
[10] Int Atom Energy Agcy MEL, Monaco, Monaco
关键词
D O I
10.1093/carcin/bgh194
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (similar to1.4) 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 (less than or equal to15 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 less than or equal to15 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.
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页码:1899 / 1909
页数:11
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