title: Striking differences in cellular catalase activity between two DNA repair-deficient diseases: xeroderma pigmentosum and trichothiodystrophy.
abstract: Xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) are two recessively transmitted human diseases characterized by DNA repair deficiency. While XP is associated with a very high incidence of cancer on skin exposed to sunlight, TTD is not a cancer-prone disease. Therefore, unrepaired UV-induced DNA lesions do not appear to be enough to give rise to tumors. In order to understand the differences between these two syndromes, we measured catalase activity in cellular extracts, UV irradiated or not, and quantified H2O2 production following in vitro UV irradiation. We confirmed on 21 different XP diploid fibroblast lines that catalase activity was decreased on average by a factor of five as compared to controls, while XP heterozygote lines exhibited intermediary responses. All seven TTD lines we tested were deficient in UV-induced lesion repair and exhibited a high level of catalase activity. However, molecular analysis of catalase transcription showed no difference between normal, XP and TTD cell lines. This was confirmed by Western blots where the amount of catalase subunits was identical in all cell lines studied. Finally, UV irradiation induces five and three times more H2O2 production in XP lines compared with TTD or controls respectively. These striking differences between TTD and XP indicate that UV light, directly or indirectly, together with defective oxidative metabolism may increase the initiation and/or the progression steps in the XP environment compared to TTD. This may partly explain the different tumoral phenotype observed between the two diseases.
authors.affiliation: URA 686 CNRS, Ecole Normale Supérieure, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Vuillaume
authors.forename: L
authors.initials: L
authors.lastname: Daya-Grosjean
authors.forename: P
authors.initials: P
authors.lastname: Vincens
authors.forename: J L
authors.initials: JL
authors.lastname: Pennetier
authors.forename: P
authors.initials: P
authors.lastname: Tarroux
authors.forename: A
authors.initials: A
authors.lastname: Baret
authors.forename: R
authors.initials: R
authors.lastname: Calvayrac
authors.forename: A
authors.initials: A
authors.lastname: Taieb
authors.forename: A
authors.initials: A
authors.lastname: Sarasin
mesh_terms: D020642:Acatalasia; D000293:Adolescent; D000328:Adult; D002374:Catalase / Q000528:radiation effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair / Q000528:radiation effects; D005260:Female; D006201:Hair Diseases / Q000201:enzymology* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009260:Nail Diseases / Q000201:enzymology* / Q000235:genetics; D010101:Oxygen Consumption / Q000528:radiation effects; D014983:Xeroderma Pigmentosum / Q000201:enzymology* / Q000235:genetics
chemical_list: D002374:Catalase