Clastogenic activity in the plasma of scleroderma patients: a biomarker of oxidative stress.
BACKGROUND
Scleroderma patients exhibit increased chromosomal instability due to circulating clastogenic plasma factors (CF). Formation and action mechanisms of CF are mediated by superoxide. In addition, previous work detected inosine triphosphate (ITP) in the plasma of 2 patients, and the enzyme adenosine deaminase (ADA) was found to be increased.


OBJECTIVE
To study correlations between CF, ITP and ADA levels, CF and disease activity, as well as other biomarkers of oxidative stress.


METHODS
Clastogenic activity was evaluated by means of cytogenetic methods in 48 patients and 55 healthy subjects. ITP was detected by mass spectrometry and electrospray ionisation. ADA was measured with a colorimetric assay and malondialdehyde using the Yagi method.


RESULTS
Clastogenic activity was significantly increased in patients' plasma compared to controls. In 10 patients CF, ITP and ADA were studied simultaneously. All three parameters were increased in the 7 patients of subgroups 2 (skin and esophagus involvement) and 3 (skin plus multiple organ involvement). ITP was not detected in 2 patients of subgroup 1 (skin involvement only) with low ADA and CF values.


CONCLUSIONS
ITP, the deamination product of ATP, is one of the clastogenic and superoxide generating components of CF. The formation of this deamination product of ATP is probably related to the increase in ADA. CF are biomarkers of oxidative stress and can be used for evaluation of antioxidant treatments in scleroderma.
Emerit
I
I
Institut Biomédical des Cordeliers, Université Paris VI, et CNRS, France.
Filipe
P
P
Meunier
P
P
Auclair
C
C
Freitas
J
J
Deroussent
A
A
Gouyette
A
A
Fernandes
A
A
D000243:Adenosine Deaminase / Q000097:blood; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003124:Colorimetry; D004563:Electrochemistry; D004935:Esophageal Diseases / Q000097:blood; D005260:Female; D006801:Humans; D007293:Inosine Triphosphate / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde; D013058:Mass Spectrometry; D008875:Middle Aged; D009153:Mutagens / Q000378:metabolism*; D018384:Oxidative Stress; D012595:Scleroderma, Systemic / Q000097:blood* / Q000188:drug therapy; D012871:Skin Diseases / Q000097:blood; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D009153:Mutagens; D013481:Superoxides; D007293:Inosine Triphosphate; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000243:Adenosine Deaminase