Effects of peroxidative stress and age on the concentration of a deoxyguanosine-malondialdehyde adduct in rat DNA.
The effect of age and peroxidative stress on the concentration of a deoxyguanosine malondialdehyde adduct (dG-MDA) in rat tissues was investigated. Vitamin E deficiency had no effect on the dG-MDA content of liver DNA in rats fed a diet containing 10% corn oil. When 2% cod liver oil was added to this diet, the dG-MDA content of liver DNA doubled in the positive controls fed a high level of vitamin E (100 ppm dl-alpha-tocopherol), and there was a further increase when vitamin E was deleted. Neither iron nitrilotriacetate administration nor choline deficiency had any effect on the dG-MDA content of liver DNA. Carbon tetrachloride had a lowering effect. The failure of iron or carbon tetrachloride administration and of vitamin E deficiency to increase liver dG-MDA is consistent with their failure in previous experiments to affect the urinary excretion of dG-MDA. In contrast, these forms of peroxidative stress produce large increments in the urinary excretion of MDA adducts with lysine, reflecting increased formation and degradation of MDA-modified proteins. DNA appears to be protected from modification by MDA produced at extranuclear sites. The frequency of dG-MDA in different tissues of 4-month-old rats varied markedly: brain >> liver > kidneys and testes. Higher concentrations of dG-MDA were found in the liver and kidneys, but not the testes, of 25-month-old rats. The determinants of the concentration of dG-MDA in DNA merit further investigation.
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
H H
HH
Draper
S
S
Agarwal
D E
DE
Nelson
J J
JJ
Wee
A K
AK
Ghoshal
E
E
Farber
D000375:Aging; D000818:Animals; D001923:Brain Chemistry; D002251:Carbon Tetrachloride / Q000494:pharmacology; D003060:Cod Liver Oil / Q000008:administration & dosage; D003314:Corn Oil / Q000008:administration & dosage; D004247:DNA / Q000032:analysis / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis*; D003849:Deoxyguanosine / Q000032:analysis* / Q000378:metabolism; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D013737:Testis / Q000737:chemistry; D014810:Vitamin E / Q000008:administration & dosage; D014811:Vitamin E Deficiency / Q000378:metabolism
D018736:DNA Adducts; D004042:Dietary Fats, Unsaturated; D014810:Vitamin E; D008315:Malondialdehyde; D003314:Corn Oil; D003060:Cod Liver Oil; D004247:DNA; D002251:Carbon Tetrachloride; D003849:Deoxyguanosine