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Reconstruction of DNA Repair–deficient Xeroderma Pigmentosum Skin In Vitro : A Model to Study Hypersensitivity to UV Light ¶
Author(s) -
Bernerd Françoise,
Asselineau Daniel,
Frechet Mathilde,
Sarasin Alain,
Magnaldo Thierry
Publication year - 2005
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2005.tb01517.x
Subject(s) - xeroderma pigmentosum , nucleotide excision repair , epidermis (zoology) , in vitro , dna repair , dna , pyrimidine dimer , skin cancer , dna damage , microbiology and biotechnology , biology , chemistry , genetics , cancer , anatomy
Xeroderma pigmentosum (XP) is a rare, recessive, photosensitive and cancer‐prone syndrome, the biochemical hallmark of which is a defect in nucleotide excision repair of ultraviolet (UV)–induced mutagenic lesions. After isolation and amplification of several strains of XP‐C keratinocytes and fibroblasts, a three‐dimensional skin model in vitro comprising both epidermis and a dermal equivalent could be obtained. XP dermal tissues and XP epidermis displayed specific morphological and biochemical characteristics compared with tissues obtained with normal cells. One of the major features was the formation of epidermal invaginations into the dermal equivalent. After UV‐B exposure, and contrary to repair of DNA lesions in normal cells, the XP model displayed repair deficiency with long‐lasting persistence of UV‐induced DNA damage and p53 positive nuclei. Recent data obtained after genetic correction leading to functional XPC gene in keratinocytes and fibroblasts revealed that several abnormal features could be normalized. In conclusion, reconstruction of XP skin in vitro provides a very promising system to study genetic hyperphotosensitivity and opens a rational perspective to XP tissue therapy.