Aberrant repair of etheno-DNA adducts in leukocytes and colon tissue of colon cancer patients

作者：Obtulowicz Tomasz; Winczura Alicja; Speina Elzbieta; Swoboda Maja; Janik Justyna; Janowska Beata; Ciesla Jaroslaw M; Kowalczyk Pawel; Jawien Arkadiusz; Gackowski Daniel; Banaszkiewicz Zbigniew; Krasnodebski Ireneusz; Chaber Andrzej; Olinski Ryszard; Nair Jagadesaan; Bartsch Helmut; Douki Thierry; Cadet Jean; Tudek Barbara^*

来源：Free Radical Biology and Medicine, 2010, 49(6): 1064-1071.

DOI：10.1016/j.freeradbiomed.2010.06.027

• Oxidative stress
• Colon cancer
• Base excision repair
• 1,N(6)-Ethenoadenine
• 3,N(4)-Ethenocytosine
• 1,N(2)-Ethenoguanine
• Free radicals

To assess the role of lipid peroxidation-induced DNA damage and repair in colon carcinogenesis, the excision rates and levels of 1,N(6)-etheno-2'-deoxyadenosine (epsilon dA), 3,N(4)-etheno-2'-deoxycytidine (epsilon dC), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilon dG) were analyzed in polymorphic blood leukocytes (PBL) and resected colon tissues of 54 colorectal carcinoma (CRC) patients and PBL of 56 healthy individuals. In PBL the excision rates of 1,N(6)-ethenoadenine (epsilon Ade) and 3,N(4)-ethenocytosine (epsilon Cyt), measured by the nicking of oligodeoxynucleotide duplexes with single lesions, and unexpectedly also the levels of epsilon dA and 1,N(2)-epsilon dG, measured by LC/MS/MS, were lower in CRC patients than in controls. In contrast the mRNA levels of repair enzymes, alkylpurine- and thymine-DNA glycosylases and abasic site endonuclease (APE1), were higher in PBL of CRC patients than in those of controls, as measured by QPCR. In the target colon tissues epsilon Ade and epsilon Cyt excision rates were higher, whereas the epsilon dA and epsilon dC levels in DNA, measured by (32)P-postlabeling, were lower in tumor than in adjacent colon tissue, although a higher mRNA level was observed only for APE1. This suggests that during the onset of carcinogenesis, etheno adduct repair in the colon seems to be under a complex transcriptional and posttranscriptional control, whereby deregulation may act as a driving force for malignancy.

• 出版日期2010-9-15
• 单位中国地震局