Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients.
Mutagenesis
; 25(5): 463-71, 2010 Sep.
Article
in En
| MEDLINE
| ID: mdl-20534734
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma
/
Adenoma
/
Colonic Neoplasms
/
Oxidative Stress
/
Deoxyguanosine
/
DNA Repair
Type of study:
Observational_studies
Language:
En
Journal:
Mutagenesis
Journal subject:
GENETICA MEDICA
/
SAUDE AMBIENTAL
Year:
2010
Document type:
Article
Affiliation country:
Poland