PMID- 15450427
OWN - NLM
STAT- MEDLINE
DCOM- 20041102
LR  - 20240109
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 554
IP  - 1-2
DP  - 2004 Oct 4
TI  - DNA damage and repair in type 2 diabetes mellitus.
PG  - 297-304
AB  - DNA damage may be associated with type 2 diabetes mellitus (T2DM) and its 
      complications mainly through oxidative stress. Little is known about DNA repair 
      disturbances potentially contributing to the overall extent of DNA damage in 
      T2DM, which, in turn, may be linked with genomic instability resulting in cancer. 
      To assess whether DNA repair may be perturbed in 2DM we determined: (1) the level 
      of endogenous basal DNA damage, this means damage recognized in the alkaline 
      comet assay (DNA strand breaks and alkali labile sites) as well as endogenous 
      oxidative and alkylative DNA damage (2) the sensitivity to DNA-damaging agents 
      hydrogen peroxide and doxorubicin and the efficacy of removing of DNA damage 
      induced by these agents in peripheral blood lymphocytes of T2DM patients and 
      healthy individuals. The level of DNA damage and the kinetics of DNA repair was 
      evaluated by the alkaline single cell gel electrophoresis (comet assay). 
      Oxidative and alkylative DNA damage were assayed with the use of DNA repair 
      enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase 
      (Fpg), recognizing oxidized DNA bases and 3-methyladenine-DNA glycosylase II 
      (AlkA) recognizing alkylated bases. The levels of basal endogenous and oxidative 
      DNA damage in diabetes patients were higher than in control subjects. There was 
      no difference between the level of alkylative DNA in the patients and the 
      controls. Diabetes patients displayed higher susceptibility to hydrogen peroxide 
      and doxorubicin and decreased efficacy of repairing DNA damage induced by these 
      agents than healthy controls. Our results suggest that type 2 diabetes mellitus 
      may be associated not only with the elevated level of oxidative DNA damage but 
      also with the increased susceptibility to mutagens and the decreased efficacy of 
      DNA repair. These features may contribute to a link between diabetes and cancer 
      and metrics of DNA damage and repair, measured by the comet assay, may be markers 
      of risk of cancer in diabetes.
FAU - Blasiak, Janusz
AU  - Blasiak J
AD  - Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237, 
      Poland. januszb@biol.uni.lodz.pl
FAU - Arabski, Michal
AU  - Arabski M
FAU - Krupa, Renata
AU  - Krupa R
FAU - Wozniak, Katarzyna
AU  - Wozniak K
FAU - Zadrozny, Marek
AU  - Zadrozny M
FAU - Kasznicki, Jacek
AU  - Kasznicki J
FAU - Zurawska, Monika
AU  - Zurawska M
FAU - Drzewoski, Jozef
AU  - Drzewoski J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
SB  - IM
MH  - Aged
MH  - Alkylation
MH  - Comet Assay
MH  - *DNA Damage
MH  - *DNA Repair
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Humans
MH  - Middle Aged
MH  - Oxidative Stress
EDAT- 2004/09/29 05:00
MHDA- 2004/11/04 09:00
CRDT- 2004/09/29 05:00
PHST- 2004/03/09 00:00 [received]
PHST- 2004/05/14 00:00 [revised]
PHST- 2004/05/19 00:00 [accepted]
PHST- 2004/09/29 05:00 [pubmed]
PHST- 2004/11/04 09:00 [medline]
PHST- 2004/09/29 05:00 [entrez]
AID - S0027510704001800 [pii]
AID - 10.1016/j.mrfmmm.2004.05.011 [doi]
PST - ppublish
SO  - Mutat Res. 2004 Oct 4;554(1-2):297-304. doi: 10.1016/j.mrfmmm.2004.05.011.