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Human keratinocyte radiosensitivity is linked to redox modulation.
Muriel Isoir1, Valérie Buard, Philippe Gasser
1Institut de Radioprotection et de Sûreté Nucléaire IRSN, Service de Radiobiologie d'Epidémiologie, Direction de la Radioprotection de l'Homme, Laboratoire de RadioPathologie, IRSN, B.P. no. 17, F-92262 Fontenay-aux-Roses Cedex, France.
Journal of Dermatological Science
|December 20, 2005
Summary
Ionizing radiation triggers reactive oxygen species (ROS) overproduction, leading to keratinocyte apoptosis. Differences in how cells manage oxidative stress influence their sensitivity to radiation therapy.
Area of Science:
- Cell Biology
- Radiation Oncology
- Dermatology
Background:
- Ionizing radiation, particularly gamma-irradiation, causes reactive oxygen species (ROS) overproduction in keratinocytes.
- This oxidative stress can lead to cellular alterations and is a common side effect of radiation therapy.
- ROS production is regulated by a complex enzymatic system within cells.
Purpose of the Study:
- To investigate the role of radiation-induced oxidative stress in keratinocyte apoptosis.
- To test the hypothesis that keratinocytes' ability to counteract ROS generation influences their radiosensitivity.
Main Methods:
- Development of a novel human skin explant model.
- Utilized primary normal human epidermal keratinocytes (NHEK) and a spontaneous non-tumorigenic cell line (HaCaT).
- Performed cDNA-array analysis, enzyme activity assays (catalase, GPx, SOD), and TUNEL labeling post-irradiation.
Main Results:
- Gamma-irradiation (20Gy) down-regulated genes involved in oxidative stress control and apoptosis.
- Observed altered enzymatic activities of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD).
- Showed differential regulation of antioxidant networks, leading to varied ROS levels and distinct radiosensitivities between keratinocyte lines, with increased apoptosis observed.
Conclusions:
- Keratinocyte apoptosis following gamma-ray exposure is partially mediated by ROS production.
- The varying radiosensitivity of keratinocytes is associated with their distinct responses to oxidative stress.