Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients
Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients
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DOI：
10.1093/mutage/geq028
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发表时间：
2010-09-01
期刊：
影响因子：
2.7
通讯作者：
Tudek, Barbara
中科院分区：
文献类型：
--
作者：
Obtulowicz, Tomasz;Swoboda, Maja;Tudek, Barbara
氧化应激参与结肠癌的发病机制。我们想阐明这种现象发生在疾病的哪个阶段。在检查的结直肠癌患者组中，（CRC，n = 89），良性腺瘤（AD，n = 77）和健康志愿者（对照组，n = 99），我们测量：血浆中的维生素A、C和E，8-氧代-7，8-二氢-2 '-脱氧鸟苷（8-oxodG）和8-氧代-7，8-二氢鸟嘌呤白细胞和尿液中的（8-oxoGua）、白细胞8-oxoGua切除活性、APE 1、OGG 1、8-oxo-7，8-dihydrodeoxyguanosine 5 '-triphosphate pyrophosphohydrolase（MTH 1）和OGG 1多态性的mRNA水平。AD和CRC患者维生素水平逐渐下降。8-CRC和AD患者的白细胞和尿液中OxodG增加。8-OxoGua仅在CRC患者的尿液中较高。8-尽管OGG 1 Cys 326 Cys基因型（编码活性降低的糖基化酶）的频率较高，但CRC患者的OxoGua切除率高于对照组。OGG 1和APE 1在CRC和AD患者中的mRNA水平增加，这可以解释CRC患者中8-oxoGua切除率增加。MTH 1 mRNA在CRC患者中也较高。结果表明，氧化应激发生在CRC和AD个体中。这伴随着CRC患者中DNA修复基因的转录增加和8-oxoGua切除率增加，然而，这不足以抵消增加的DNA损伤。
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.