Human keratinocyte radiosensitivity is linked to redox modulation

• Published in: Journal of dermatological science Vol. 41; no. 1; pp. 55 - 65
• Main Authors: Isoir, Muriel, Buard, Valérie, Gasser, Philippe, Voisin, Philippe, Lati, Elian, Benderitter, Marc
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01-01-2006; Elsevier
• Subjects: Adult; Apoptosis; Apoptosis - radiation effects; Catalase - metabolism; Cell Line, Transformed; Epidermis - cytology; Female; Gene Expression Profiling; Glutathione Peroxidase - metabolism; Humans; Ionising radiation; Keratinocyte; Keratinocytes - cytology; Keratinocytes - enzymology; Keratinocytes - radiation effects; Life Sciences; Oxidation-Reduction - radiation effects; Oxidative stress; Oxidative Stress - radiation effects; Radiation, Ionizing; Radiosensitivity; Reactive Oxygen Species - radiation effects; Skin; Superoxide Dismutase - metabolism; Oxidative stress; Keratinocyte; Skin; Radiosensitivity; Ionising radiation; Apoptosis; gamma radiation; oxidation reduction reaction; Reactive Oxygen Species; Humans; Radiation; epidermis cell; apoptosis; Gene Expression Profiling; complementary DNA; Transformed; DNA determination; enzyme activity; Ionizing; Adult; Female; priority journal; radiation dose; cell line; human; catalase; nick end labeling; Oxidation-Reduction; radiosensitivity; Keratinocytes; Epidermis; human cell; article; nucleotide sequence; controlled study; keratinocyte; superoxide dismutase; down regulation; oxidative stress; glutathione peroxidase; reactive oxygen metabolite
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2005.11.008

Ionising radiation-induced reactive oxygen species (ROS) overproduction induces keratinocyte alterations and constitutes one of the most common effects after therapeutic γ-irradiation. ROS production is controlled by a complex enzymatic system.
The aim of our study is to analyse the role of radiation-induced oxidative stress in keratinocytes death by apoptosis. We hypothesized that keratinocyte capacity to hamper radiation-induced ROS generation may control their radiosensitivity.
For this purpose, an original human skin explant model was developed and two types of human epidermal cells were used: primary keratinocytes NHEK and spontaneous non-tumourigenic cell line HaCaT.
cDNA-arrays analysis was performed 24
h after a 20
Gy γ-radiation and revealed down-regulation of genes involved in oxidative stress control and the apoptosis process. This was confirmed by alterations in catalase, GPx and SOD enzymatic activities. This redox modulation was concomitant to the down-regulation of anti-apoptotic genes and up-regulation of some pro-apoptotic genes (caspase 10, ubiquitin C). Interestingly TUNEL labelling revealed an increase in the number of apoptotic cells. We also demonstrated a differential inducibility of the cell antioxidant network in two keratinocyte lines, which results in a differential cellular level of ROS, explaining their different radiosensitivities.
Keratinocytes apoptosis is partly dependent on ROS production after exposure to γ-rays. In addition, the differential radiosensitivity of keratinocytes is linked to different oxidative stress responses.