Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients.
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.
Obtulowicz
Tomasz
T
Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland.
Swoboda
Maja
M
Speina
Elzbieta
E
Gackowski
Daniel
D
Rozalski
Rafal
R
Siomek
Agnieszka
A
Janik
Justyna
J
Janowska
Beata
B
Ciesla
Jaroslaw M
JM
Jawien
Arkadiusz
A
Banaszkiewicz
Zbigniew
Z
Guz
Jolanta
J
Dziaman
Tomasz
T
Szpila
Anna
A
Olinski
Ryszard
R
Tudek
Barbara
B
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000236:Adenoma / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D018256:Adenomatous Polyps / Q000097:blood / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics; D000975:Antioxidants / Q000378:metabolism; D002277:Carcinoma / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018384:Oxidative Stress / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
D000975:Antioxidants; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C078207:8-oxodGTPase; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine