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.