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

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.

Inflammation and Pyroptosis Mediate Muscle Expansion in an Interleukin-1β (IL-1β)-dependent Manner

“…3), enabling the activation of NLRP3 in signal II (43,44). Acrolein-mediated transcription silencing by promoter methylation of OGG1 resulted in reduced capacity to repair 8-oxo-dG (28,31,32). Activated NLRP3 can stimulate the complex with apoptosis-associated speck-like protein containing CARD (ASC) to cause the proteolytic maturation of caspase-1 (45).…”

“…Nicotinamide reactivated only three base excision repair genes, Neil1 (p value Ͻ 0.01), Ogg1 (p value Ͻ 0.05), and Parp1 (p value Ͻ 0.01), as well as a homologous recombination repair gene, Rad50 (p value Ͻ 0.001). The epigenetic silencing of Ogg1, responsible for mitochondrial DNA damage repair, could support the accumulation of 8-oxo-dG for associated NLRP3-mediated caspase 1 activation (28,31,32).…”

XRCC1 rs25487 polymorphism is associated with lung cancer risk in epidemiologically susceptible Chinese people

“…Interestingly, we found that OGG1 rs1052133-GG was associated with early age of lung cancer onset. Some studies examining the relationship between the OGG1 Ser326Cys genotype and BER repair activity or OGG1 expression have revealed that the OGG1 Ser326Cys polymorphism is not associated with differences in repair capacity or OGG1 expression (Janssen et al, 2001(Janssen et al, , 2012, whereas other studies have reported that the Ser326Cys genotype causes substantially decreased repair activity or higher mRNA levels of OGG1 (Vodicka et al, 2007;Hatt et al, 2008;Obtulowicz et al, 2010). Thus, based on the literature, we cannot draw conclusions regarding the association between the OGG1 Ser326Cys polymorphism and the level of DNA damage and repair capacity of BER in the general population.…”

“…Moreover, conflicting results have been reported for the association of the XRCC1 Arg399Gln polymorphism and lung cancer risk (Zhou et al, 2003;Popanda et al, 2004;Matullo et al, 2006;Ryk et al, 2006). Similarly, inconclusive results have been obtained for the OGG1 Ser326Cys polymorphism regarding its association with cancer (Janssen et al, 2001;Vodicka, et al, 2007;Hatt et al, 2008;Obtulowicz et al, 2010;Jensen et al, 2012). In addition, little is known regarding the relationship between the PARP1 rs1136410 (Val762Ala) polymorphism and lung cancer risk (Zhang et al, 2005).…”

Colorectal Cancer and the Preventive Effects of Food Components

“…In colorectal cancer patients, the level of vitamin A, vitamin C, and vitamin E were reduced, and urinary 8-oxo-dG, a biomarker of DNA oxidation, was elevated (Obtulowicz et al, 2010).…”