Skin cancer: Reconstruction of xeroderma pigmentosum skin

Paris, July 16, 2001

CNRS/L'Oréal Press Release

For the first time, xeroderma pigmentosum (XP) skin has been successfully reconstructed in vitro by CNRS researchers from the "Laboratoire instabilité génétique et cancer" (Genetic Instability and Cancer Unit) and the L’Oréal Life Sciences Department. Patients with this hereditary disease, which is rare but often fatal, are prone to skin cancer induced by UV radiation from sunlight. The possibility of studying the molecular mechanics of XP skin opens up major pharmacological, cosmetological, and therapeutic prospects.

Skin cancer is the most frequent type of tumor in humans. The incidence increases with exposure to sunlight, the ultraviolet (UV) radiation contained in sunlight being the main culprit. It causes damage to the DNA of exposed cells, in particular those making up the surface layer of our skin, the epidermis. In normal individuals, such damage is repaired by a system specialized in repairing DNA, thereby preserving our genetic heritage. However, if such damage persists, it can lead to mutations (modification of the DNA) and potentially to the development of skin cancer. In patients suffering from a rare genetic disease known as xeroderma pigmentosum (XP), the structure of certain genes involved in the DNA repair process is deficient. Continued damage to the DNA, induced by UV radiation from sunlight, gives rise to severe intolerance to the sun, together with a dramatic proneness to skin cancer, which is nearly always the cause of the premature death of patients.

On the basis of small skin samples taken from consenting patients, the researchers have developed a technique for reconstructing and cultivating XP skin in vitro. Such skin has very high sensitivity to ultraviolet radiation, and has also revealed previously undocumented degradation in cell differentiation and multiplication, which might play a part in the carcinogenic process. The development of this first system for reconstructing human skin that is hypersensitive to ultraviolet radiation will enable the early carcinogenic molecular and cellular mechanisms of skin cancer to be studied in detail within the tissue itself.

This research has opened up numerous pharmacological, cosmetological, and therapeutic prospects for improving the prevention and treatment of skin cancer, not only in DNA repair-deficient XP patients, but also in the general population, which is broadly affected by the adverse effects of the sun.

Reference
F. Bernerd, D. Asselineau, C. Vioux, O. Chevallier-Lagente, B. Bouadjar, A. Sarasin et T. Magnaldo. "Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro." Proceedings of the National Academy of Sciences, 98, 3, July 2001, pp 7817-7822.

Researcher contacts:
Thierry Magnaldo, CNRS chargé de recherche
and Alain Sarasin, CNRS Research Director
"Laboratoire Étude des relations instabilité génétique et cancer" (Genetic Instability and Cancer Unit, CNRS – Villejuif)
Tel: 33 1 49 58 34 20
e-mail: magnaldo@infobiogen.fr
e-mail: sarasin@infobiogen.fr
L'Oréal researcher contacts:
Françoise Bernerd and Daniel Asselineau
L'Oréal Recherche - Centre de recherche C. Zviak - Clichy
Tel: 33 1 47 56 73 27
e-mail: fbernerd@recherche.loreal.com

Communications contact, CNRS Department of Life Sciences:
Marie-Pascale Corneloup-Brossollet
Tel: 33 1.44.96 46 48
e-mail: marie.corneloup@cnrs-dir.fr
CNRS Press contact:
Martine Hasler
Tel: 33 1 44 96 46 35
e-mail: martine.hasler@cnrs-dir.fr
L'Oréal Recherche Press contact:
Isabelle Walter
Tel : 33 1 47 56 71 63
e-mail: iwalter@recherche.loreal.com