Lj. Hardie et al., The effect of hOGG1 and glutathione peroxidase I genotypes and 3p chromosomal loss on 8-hydroxydeoxyguanosine levels in lung cancer, CARCINOGENE, 21(2), 2000, pp. 167-172
Polymorphic genes for the peroxide scavenger glutathione thione peroxidase
I (GPX1) and 8-hydroxydeoxyguanosine (8-OHdG) DNA glycosylase/apurinic (AP)
lyase (hOGG1) map to loci on chromosome 3p which are subject to frequent l
oss of heterozygosity (LOH) in lung tumours, Levels of the pro-mutagenic, o
xidative DNA lesion 8-OHdG, were measured in 37 paired normal and tumorous
lung specimens using HPLC with electrochemical detection, Lung tumours were
also analysed for 3p LOH by fluorescent PCR with Genescan analysis. No sig
nificant difference was observed between 8-OHdG levels in tumour [7.7 +/- 6
.7 (mean +/- SE) 8-OHdG/10(6) 2'-deoxyguanosine (dG)] and normal (8.1 +/- 8
.8 8-OHdG/10(6) dG) lung tissue. Adduct levels in normal lung tissue DNA we
re not associated with constitutive hOGG1 genotype although there was a tre
nd towards lower 8-OHdG levels in individuals possessing the ALA6 GPX1 poly
morphism. Lung tumours exhibiting 3p LOH (40%) contained higher levels of 8
-OHdG adducts (10.9 +/- 2.6 8-OHdG/10(6) dG) (P = 0.05) and lower GPX1 enzy
me activity [45.5 nmol glutathione (GSH)/min/mg] (P = 0.09) when compared w
ith tumours without LOH at these sites (5.55 +/- 0.87 8-OHdG/106 dG and 63.
6 nmol GSH/min/mg, respectively). In conclusion, tumours with 3p LOH at loc
i associated with hOGG1 and GPX1 appear to have compromised oxidative defen
ce mechanisms as measured by reduced GPX1 enzyme activity and elevated 8-OH
dG levels and this may affect the prognosis of lung cancer patients.