Age-dependent DNA repair and cell cycle distribution of human skin fibroblasts in response to UVA irradiation.
Ageing process in cells is associated with oxidative stress. Ultraviolet A produces reactive oxygen species responsible for accumulation of DNA and cellular damage. After the evaluation of antioxidant enzyme activities and oxidative stress markers at the basal state, we have studied the responses to UVA stress of coetaneous fibroblasts, isolated from different male donors (2-88 years, n=23) in terms of cytotoxicity, genotoxicity and DNA repair capacities. For this purpose, we have determined level of DNA damage using the comet assay (single strand breaks and alkali-labile sites) and the cell cycle distribution after a 5 J/cm2 irradiation. No differences with age were observed for antioxidant enzyme activities and oxidative stress markers. DNA strand breaks after UVA irradiation (5-20 J/cm2), was found to be age-dependent. DNA repair was slow and also significantly affected by ageing. The cell cycle distribution analysis showed that high repair correlated with high proliferative capacities at basal level. Twenty-four hours after the stress, fraction of young fibroblasts blocked in G1 phase was significantly increased whereas significant modifications concerned the G2-M phase for adult and older fibroblasts. These results indicate an age-dependent decline in the DNA repair capacities correlated with modifications of the cell cycle parameters.
Hazane
Florence
F
Laboratoire Oligoéléments et Résistance au Stress Oxydant induit par les Xénobiotiques (Laboratoire ORSOX - UMR-E3 UJF/CEA) Université Joseph Fourier, UFR de Médecine et Pharmacie, Domaine de la Merci, 38700 La Tronche, France.
Sauvaigo
Sylvie
S
Douki
Thierry
T
Favier
Alain
A
Beani
Jean-Claude
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000975:Antioxidants / Q000378:metabolism; D002453:Cell Cycle / Q000528:radiation effects*; D002648:Child; D002675:Child, Preschool; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
D000975:Antioxidants