Carcinogenesis Advance Access originally published online on June 10, 2004
Carcinogenesis 2004 25(10):1899-1909; doi:10.1093/carcin/bgh194
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Carcinogenesis vol.25 no.10 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Gender- and age-related distinctions for the in vivo prooxidant state in Fanconi anaemia patients
k71 Italian National Cancer Institute, ‘G. Pascale’ Foundation, Via M.Semmola 12, I-80131 Naples, Italy, 2 Italian National Cancer Institute, IST, Genoa, Italy, 3 Department of Organic Chemistry and Biochemistry, Federico II Naples University, Naples, Italy, 4 Division of Life Sciences, King's College, London, UK, 5 Department of Physiology, University of Valencia, Valencia, Spain, 6 Department of Genetics, Elena d'Aosta Hospital, ASL Napoli 1, Naples, Italy, 7 Department of Paediatric Haematology, Istanbul University, Istanbul, Turkey, 8 Department of Paediatrics, 2nd Naples University, Naples, Italy, 9 Department of Paediatrics, Cardarelli Hospital, Naples, Italy and 10 International Atomic Energy Agency–MEL, Monaco
11 To whom correspondence should be addressed Email: gbpagano{at}tin.it
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 (
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 (
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 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.
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