Oxidized guanine lesions and hOgg1 activity in lung cancer.
In humans, the oxidatively induced DNA lesion 8-hydroxyguanine (8-oxoG) is removed from DNA by hOgg1, a DNA glycosylase/AP lyase that specifically incises 8-oxoG opposite cytosine. We analysed the expression of hOGG1 mRNA in 18 lung cancer and three normal cell lines. Although hOGG1 was overexpressed in most cell lines, 2/18 (11.1%) showed a lower hOGG1 mRNA and protein expression (approximately 80% decrease) relative to normal cell lines. Liquid chromatography/mass spectrometry analysis showed increased levels of 8-oxoG in the two cell lines with the lowest hOGG1 mRNA expression. We examined the ability of nuclear and mitochondrial extracts to incise 8-oxoG lesion in cell lines H1650 and H226 expressing lower hOGG1 mRNA and H1915 and H1975 with higher than normal hOGG1 mRNA expression. Both nuclear and mitochondrial extracts from H1915 and H1975 cells were proficient in 8-oxoG removal. However, both cell lines with the lowest hOGG1 mRNA expression exhibited a severe reduction in 8-oxoG incision in both nuclear and mitochondrial extracts. Under-expression of hOGG1 mRNA and hOgg1 protein was associated with a decrease in mitochondrial DNA repair in response to oxidative damaging agents. These results provide evidence for defective incision of 8-oxoG in both nuclear and mitochondria of H1650 and H226 lung cancer cell lines. These results may implicate 8-oxoG repair defects in certain lung cancers.
Mambo
Elizabeth
E
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Chatterjee
Aditi
A
de Souza-Pinto
Nadja C
NC
Mayard
Sabine
S
Hogue
Barbara A
BA
Hoque
Mohammad O
MO
Dizdaroglu
Miral
M
Bohr
Vilhelm A
VA
Sidransky
David
D
D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D004249:DNA Damage / Q000502:physiology; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D012016:Reference Values; D017421:Sequence Analysis; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D016877:Oxidants; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human