Radical production in liver mitochondria by peroxidic tumor promoters.
Eleven peroxides have been tested to determine if there is a correlation between tumor-promoting activity and the ability to stimulate radical production in mitochondria. When non-respiring rat liver mitochondria are treated with these peroxidic compounds in the presence of DMPO, ESR signals are observed from the spin trapping of carbon- and oxygen-centered radicals in the case of 4 of the 7 peroxides that are known to be tumor promoters. Enhancement of carbon-centered radical production is observed in the presence of respiratory substrate. Thus there does not appear to be a correlation between tumor-promoting activity of peroxidic compounds and radical production in mitochondria. Oxidants can act as promoters either by 1- or 2-electron oxidation pathways; both types of mechanisms may be inhibited by antioxidants, which can scavenge either radicals or electrophiles.
Kennedy
C H
CH
Biodynamics Institute, Louisiana State University, Baton Rouge 70803.
Dyer
J M
JM
Church
D F
DF
Winston
G W
GW
Pryor
W A
WA
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D005609:Free Radicals; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010545:Peroxides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D003497:Cyclic N-Oxides; D005609:Free Radicals; D010545:Peroxides; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D010100:Oxygen