Induction and rejoining of DNA single-strand breaks in relation to cellular growth in human cells exposed to three hydroperoxides at 0 degrees C and 37 degrees C.
There was a 5-fold increase in cytotoxicity for cumene hydroperoxide, 10-fold for tert-butyl hydroperoxide and 25-fold for hydrogen peroxide, under metabolizing conditions (37 degrees C) in comparison to nonmetabolizing conditions (0 degrees C), when human P31 cells were exposed for 60 min. The induction of DNA single-strand breaks correlated poorly with cytotoxicity. Hydrogen peroxide was by far the most effective agent inducing single-strand breaks irrespective of temperature. Cumene hydroperoxide produced fewer strand breaks than tert-butyl hydroperoxide despite its greater cytotoxicity at either 37 degrees C or at 0 degrees C. The pattern of single-strand break induction did not change with temperature. The number of breaks, however, increased when the cells were exposed at 37 degrees C. The pattern of rejoining was similar for hydrogen peroxide- and tert-butyl hydroperoxide-induced breaks at both temperatures whereas the rejoining of cumene hydroperoxide-induced breaks deviated somewhat from this pattern. The results indicate that there is no clear-cut relationship between induction of DNA single-strand breaks and cytotoxicity after hydroperoxide exposure.
Sandström
B E
BE
Division of Ionizing Radiation and Fallout, National Defence Research Establishment, Umeå, Sweden.
D001555:Benzene Derivatives / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005609:Free Radicals; D005720:Gamma Rays; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D008654:Mesothelioma / Q000473:pathology; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology*; D013696:Temperature; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D020122:tert-Butylhydroperoxide
D001555:Benzene Derivatives; D004273:DNA, Neoplasm; D005609:Free Radicals; D010545:Peroxides; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; C007164:cumene hydroperoxide