title: Aberrant repair of etheno-DNA adducts in leukocytes and colon tissue of colon cancer patients.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Obtułowicz
authors.forename: Alicja
authors.initials: A
authors.lastname: Winczura
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Speina
authors.forename: Maja
authors.initials: M
authors.lastname: Swoboda
authors.forename: Justyna
authors.initials: J
authors.lastname: Janik
authors.forename: Beata
authors.initials: B
authors.lastname: Janowska
authors.forename: Jarosław M
authors.initials: JM
authors.lastname: Cieśla
authors.forename: Paweł
authors.initials: P
authors.lastname: Kowalczyk
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Jawien
authors.forename: Daniel
authors.initials: D
authors.lastname: Gackowski
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Banaszkiewicz
authors.forename: Ireneusz
authors.initials: I
authors.lastname: Krasnodebski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Chaber
authors.forename: Ryszard
authors.initials: R
authors.lastname: Olinski
authors.forename: Jagadesaan
authors.initials: J
authors.lastname: Nair
authors.forename: Helmut
authors.initials: H
authors.lastname: Bartsch
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.forename: Barbara
authors.initials: B
authors.lastname: Tudek
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018736:DNA Adducts / Q000378:metabolism; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D003839:Deoxyadenosines / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D044502:Thymine DNA Glycosylase / Q000235:genetics / Q000378:metabolism*
chemical_list: C115182:1,N(6)-etheno-2'-deoxyadenosine; D018736:DNA Adducts; D003839:Deoxyadenosines; D003841:Deoxycytidine; C032222:3,N(4)-ethenodeoxycytidine; D045647:DNA Glycosylases; D044502:Thymine DNA Glycosylase; C076131:DNA-3-methyladenine glycosidase II; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase