The effect of hydrogen peroxide/L-histidine-induced DNA single- vs. double-strand breaks on poly(ADP-ribose)polymerase.
L-Histidine markedly increases the ability of hydrogen peroxide to induce DNA cleavage and this effect is associated with a 3-aminobenzamide-inhibitable decline in NAD+ levels, an event which very likely reflects an enhanced stimulation of the enzyme poly(ADP-ribose)polymerase. 3-Aminobenzamide slowed down the removal of alkaline elution-detected strand breaks induced by either H2O2 alone (producing only DNA single-strand breaks) or associated with L-histidine (resulting in the formation of both single-strand breaks and DNA double-strand breaks), and the extent of inhibition was similar under the two experimental conditions. 3-Aminobenzamide did not affect the rate of rejoining of DNA double-strand breaks generated by the cocktail H2O2/L-histidine. The above results suggest that these double-strand breaks have hardly any effect on the induction of poly(ADP-ribose)polymerase activity, a conclusion that is consistent with the observation that the activity of this enzyme appears to be basically identical under conditions that abolish the formation of DNA double-strand breaks, in the absence of measurable variations in the level of induction of DNA single-strand breaks (e.g. in the presence of an excess of L-glutamine, a competitive inhibitor of L-histidine uptake). Finally, 3-aminobenzamide did not affect the toxicity of the oxidant, both in the absence and presence of L-histidine.
Palomba
L
L
Institute of Pharmacology and Pharmacognosy, University of Urbino, Italy.
Guidarelli
A
A
Cattabeni
F
F
Cantoni
O
O
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D013997:Time Factors
D018698:Glutamic Acid; D006639:Histidine; D004247:DNA; D006861:Hydrogen Peroxide; D004259:DNA-Directed DNA Polymerase