PMID- 20600828 OWN - NLM STAT- MEDLINE DCOM- 20110315 LR - 20131121 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 49 IP - 6 DP - 2010 Sep 15 TI - Aberrant repair of etheno-DNA adducts in leukocytes and colon tissue of colon cancer patients. PG - 1064-71 LID - 10.1016/j.freeradbiomed.2010.06.027 [doi] AB - 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 (epsilondA), 3,N(4)-etheno-2'-deoxycytidine (epsilondC), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilondG) 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 (epsilonAde) and 3,N(4)-ethenocytosine (epsilonCyt), measured by the nicking of oligodeoxynucleotide duplexes with single lesions, and unexpectedly also the levels of epsilondA and 1,N(2)-epsilondG, 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 epsilonAde and epsilonCyt excision rates were higher, whereas the epsilondA and epsilondC 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. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Obtulowicz, Tomasz AU - Obtulowicz T AD - Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland. FAU - Winczura, Alicja AU - Winczura A FAU - Speina, Elzbieta AU - Speina E FAU - Swoboda, Maja AU - Swoboda M FAU - Janik, Justyna AU - Janik J FAU - Janowska, Beata AU - Janowska B FAU - Ciesla, Jaroslaw M AU - Ciesla JM FAU - Kowalczyk, Pawel AU - Kowalczyk P FAU - Jawien, Arkadiusz AU - Jawien A FAU - Gackowski, Daniel AU - Gackowski D FAU - Banaszkiewicz, Zbigniew AU - Banaszkiewicz Z FAU - Krasnodebski, Ireneusz AU - Krasnodebski I FAU - Chaber, Andrzej AU - Chaber A FAU - Olinski, Ryszard AU - Olinski R FAU - Nair, Jagadesaan AU - Nair J FAU - Bartsch, Helmut AU - Bartsch H FAU - Douki, Thierry AU - Douki T FAU - Cadet, Jean AU - Cadet J FAU - Tudek, Barbara AU - Tudek B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100628 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (1,N(6)-etheno-2'-deoxyadenosine) RN - 0 (DNA Adducts) RN - 0 (Deoxyadenosines) RN - 0W860991D6 (Deoxycytidine) RN - 68498-26-0 (3,N(4)-ethenodeoxycytidine) RN - EC 3.2.2.- (DNA Glycosylases) RN - EC 3.2.2.- (Thymine DNA Glycosylase) RN - EC 3.2.2.21 (DNA-3-methyladenine glycosidase II) RN - EC 4.2.99.18 (APEX1 protein, human) RN - EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase) SB - IM MH - Adult MH - Aged MH - Carcinoma/*genetics/metabolism/pathology/physiopathology MH - Case-Control Studies MH - Colon/*metabolism/pathology MH - Colonic Neoplasms/*genetics/metabolism/pathology/physiopathology MH - DNA Adducts/metabolism MH - DNA Glycosylases/genetics/*metabolism MH - DNA Repair/genetics MH - DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics/*metabolism MH - Deoxyadenosines/metabolism MH - Deoxycytidine/analogs & derivatives/metabolism MH - Female MH - Humans MH - Leukocytes, Mononuclear/*metabolism/pathology MH - Lipid Peroxidation MH - Middle Aged MH - Mutation/genetics MH - Thymine DNA Glycosylase/genetics/*metabolism EDAT- 2010/07/06 06:00 MHDA- 2011/03/16 06:00 CRDT- 2010/07/06 06:00 PHST- 2009/08/07 00:00 [received] PHST- 2010/06/07 00:00 [revised] PHST- 2010/06/21 00:00 [accepted] PHST- 2010/07/06 06:00 [entrez] PHST- 2010/07/06 06:00 [pubmed] PHST- 2011/03/16 06:00 [medline] AID - S0891-5849(10)00392-8 [pii] AID - 10.1016/j.freeradbiomed.2010.06.027 [doi] PST - ppublish SO - Free Radic Biol Med. 2010 Sep 15;49(6):1064-71. doi: 10.1016/j.freeradbiomed.2010.06.027. Epub 2010 Jun 28.