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Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients.

Obtułowicz, Tomasz and Swoboda, Maja and Speina, Elzbieta and Gackowski, Daniel and Rozalski, Rafał and Siomek, Agnieszka and Janik, Justyna and Janowska, Beata and Cieśla, Jarosław M. and Jawien, Arkadiusz and Banaszkiewicz, Zbigniew and Guz, Jolanta and Dziaman, Tomasz and Szpila, Anna and Oliński, Ryszard and Tudek, Barbara (2010) Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients. Mutagenesis, 25 (5). pp. 463-71. ISSN 1464-3804



Oxidative stress is involved in the pathogenesis of colon cancer. We wanted to elucidate at which stage of the disease this phenomenon occurs. In the examined groups of patients with colorectal cancer (CRC, n = 89), benign adenoma (AD, n = 77) and healthy volunteers (controls, n = 99), we measured: vitamins A, C and E in blood plasma, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in leukocytes and urine, leukocyte 8-oxoGua excision activity, mRNA levels of APE1, OGG1, 8-oxo-7,8-dihydrodeoxyguanosine 5'-triphosphate pyrophosphohydrolase (MTH1) and OGG1 polymorphism. The vitamin levels decreased gradually in AD and CRC patients. 8-OxodG increased in leukocytes and urine of CRC and AD patients. 8-OxoGua was higher only in the urine of CRC patients. 8-OxoGua excision was higher in CRC patients than in controls, in spite of higher frequency of the OGG1 Cys326Cys genotype, encoding a glycosylase with decreased activity. mRNA levels of OGG1 and APE1 increased in CRC and AD patients, which could explain increased 8-oxoGua excision rate in CRC patients. MTH1 mRNA was also higher in CRC patients. The results suggest that oxidative stress occurs in CRC and AD individuals. This is accompanied by increased transcription of DNA repair genes, and increased 8-oxoGua excision rate in CRC patients, which is, however, insufficient to counteract the increased DNA damage.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Molecular Biology
ID Code:91
Deposited By: Dr Elżbieta Speina
Deposited On:16 Mar 2011 06:29
Last Modified:01 Oct 2015 07:37

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