Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer

Citation
Yj. Park et al., Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer, EUR J CANC, 37(3), 2001, pp. 340-346
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
EUROPEAN JOURNAL OF CANCER
ISSN journal
0959-8049 → ACNP
Volume
37
Issue
3
Year of publication
2001
Pages
340 - 346
Database
ISI
SICI code
0959-8049(200102)37:3<340:GCOHAT>2.0.ZU;2-P
Abstract
oh8Gua glycosylase repairs DNA by removing oh8Gua, a highly mutagenic oxida tive DNA adduct. Recently, the gene for human oh8Gua glycosylase (hOGG1) wa s cloned and several mutational types have been reported. However, the impl ications of such mutations in human cancer have not been clearly demonstrat ed. To test the involvement of hOGG1 mutation in colon carcinogenesis, we a nalysed the genetic changes of hOGG1 and the activity of oh8Gua glycosylase in 15 paired normal and tumorous colon specimens. The activity of antioxid ant enzymes (catalase and superoxide dismutase (SOD)) and extent of oxidati ve cellular damage (oh8Gua and malondialdehyde) were also assessed to compa re the oxidative status of normal and tumour tissues. An Arg 154 to His mut ation was detected in two tumour samples, but not in the corresponding norm al tissues. A Ser 326 to Cys mutation (polymorphism) was found in both the normal and tumour tissues of 3 patients. However, neither the Arg 154 to Hi s mutation nor the polymorphism at codon 326 significantly decreased the oh 8Gua glycosylase activity. The mean activity of oh8Gua glycosylase was sign ificantly higher in the tumours than in normal tissues (P = 0.022). Antioxi dant enzyme activities were decreased (catalase; P = 0.004 and SOD; P = 0.0 02), and the extent of oxidative damage correspondingly increased in the tu mour tissues (oh8Gua; P = 0.007 and malondialdehyde; P = 0.046). Although t he sample size was limited, these results suggest that the somatic mutation or the polymorphism of hOGG1 is less likely to be involved in colon carcin ogenesis. Nevertheless, the greater oxidative DNA damage in the tumour tiss ues, as a possible result of impaired antioxidant activity, implies an impo rtant role for oxygen free-radicals in colon carcinogenesis. (C) 2001 Elsev ier Science Ltd. All rights reserved.