DNA damage and apoptosis in mononuclear cells from glucose-6-phosphate dehydrogenase-deficient patients (G6PD Aachen variant) after UV irradiation.
Patients affected with X chromosome-linked, hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency suffer from life-threatening hemolytic crises after intake of certain drugs or foods. G6PD deficiency is associated with low levels of reduced glutathione. We analyzed mononuclear white blood cells (MNC) of three males suffering from the German G6PD Aachen variant, four heterozygote females of this family, one G6PD-deficient male from another family coming from Iran, and six healthy male volunteers with respect to their DNA damage in two different genes (G6PD and T-cell receptor-delta) and their propensity to enter apoptosis after UV illumination (0.08-5.28 J/cm2). As determined by PCR stop assays, there was more UV-induced DNA damage in MNC of G6PD-deficient male patients than in those of healthy subjects. MNC of G6PD-deficient patients showed a higher rate of apoptosis after UV irradiation than MNC of healthy donors. MNC of heterozygote females showed intermediate rates of DNA damage and apoptosis. It is concluded that increased DNA damage may be a result of deficient detoxification of reactive oxygen species by glutathione and may ultimately account for the higher rate of apoptosis in G6PD-deficient MNC.
Efferth
T
T
Department for Internal Medicine IV, University Hospital, Aachen, Germany.
Fabry
U
U
Osieka
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000528:radiation effects*; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D005260:Female; D019676:Genes, T-Cell Receptor delta / Q000235:genetics / Q000528:radiation effects; D014644:Genetic Variation; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005978:Glutathione / Q000097:blood; D006579:Heterozygote; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004247:DNA; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione