Age-dependent increase of etheno-DNA-adducts in liver and brain of ROS overproducing OXYS rats.
Reactive oxygen species (ROS) and lipid peroxidation (LPO) play a role in aging and degenerative diseases. To correlate oxidative stress and LPO-derived DNA damage, we determined etheno-DNA-adducts in liver and brain from ROS overproducing OXYS rats in comparison with age-matched Wistar rats. Liver DNA samples from 3- and 15-month-old OXYS and Wistar rats were analyzed for 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) by immunoaffinity/32P-postlabelling. While epsilondA and epsilondC levels were not different in young rats, adduct levels were significantly higher in old OXYS rats when compared to old Wistar or young OXYS rats. Frozen rat brain sections were analyzed for epsilondA by immunostaining of nuclei. Brains from old OXYS rats accumulated epsilondA more frequently than age-matched Wistar rats. Our results demonstrate increased LPO-induced DNA damage in organs of OXYS rats which correlates with their known shorter life-span and elevated frequency of chronic degenerative diseases.
Nair
Jagadeesan
J
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Sinitsina
Olga
O
Vasunina
Elena A
EA
Nevinsky
Georgy A
GA
Laval
Jacques
J
Bartsch
Helmut
H
D000375:Aging / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism*; D003839:Deoxyadenosines / Q000235:genetics / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D018736:DNA Adducts; D003839:Deoxyadenosines; D017382:Reactive Oxygen Species; D003841:Deoxycytidine; C032221:1,N(6)-ethenodeoxyadenosine; C032222:3,N(4)-ethenodeoxycytidine