Speaker
Dr
Michele Martin
(Laboratory of Genomics and Radiobiology of Keratinopoiesis, CEA, Evry, France)
Description
Skin is a well-known target of ionizing radiation as both complications in normal tissues and radiation-induced cancers have been documented, mainly developing from epidermis. Human epidermis is constantly renewed over a cycle of 28 days. This short-term constant renewal is due to a specific type of cells called the keratinocyte progenitors. They are located in the deepest layer of epidermis, or basal layer. These progenitors are highly sensitive to ionizing radiation (1), thus responsible for the short-term effects of radiation, such as radiodermatitis, dry and moist desquamation. Moreover, the progenitors that have resisted to radiation exposure exhibit a reduced capacity of DNA damage repair (2) and a long standing genomic instability. Keratinocyte progenitors appear thus to be a major target for cancer formation in skin. The long-term maintenance of skin homeostasis is due to rare (0.2%) and dormant stem cells, also located in the basal layer of epidermis. We demonstrated that keratinocyte stem cells are radioresistant (1) and possess a high capacity of repair for all types of DNA damage (2). Moreover, stem cells have developed specific mechanisms of protection against genotoxic stress, including modification of their niche through the FGF2 growth factor (2; 3). Thus stem cell response to radiation appears to favour long-term tissue maintenance. However, as the error prone repair pathway NHEJ might be the main repair mechanisms in stem cells, tissue maintenance might be at the expense of genomic stability and overall stem cell response favour cancer formation (4). In skin, the fact that all basal cells appear to be direct targets of genotoxic stresses might explain why skin carcinoma is one of the most frequent tumour types in humans. To further explore this high cancer susceptibility, we are currently investigating how the mechanisms of genomic stability maintenance differ between stem cells from normal individuals versus radiosensitive patients.
1- Rachidi W et al. Radiotherapy and Oncology, 2007, 83, 267-276.
2- Harfouche G et al. Stem Cells, 2010, 28:1639–1648.
3- Marie M et al., Int J Radiat Biol, 2012, in press.
4- Harfouche G et al. Mutation Research Review, 2010, 704: 167–174.
Primary author
Dr
Michele Martin
(Laboratory of Genomics and Radiobiology of Keratinopoiesis, CEA, Evry, France)
