title: High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene.
abstract: Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.
authors.affiliation: Institute for Molecular and Cellular Biology, Osaka University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakane
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Yuba
authors.forename: M
authors.initials: M
authors.lastname: Saijo
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: H
authors.initials: H
authors.lastname: Murai
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatsuru
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: S
authors.initials: S
authors.lastname: Hirota
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein
chemical_list: D004268:DNA-Binding Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D015127:9,10-Dimethyl-1,2-benzanthracene