RT Journal Article
SR Electronic
T1 Evidence for dissimilar mechanisms of enhancement of inorganic and organic hydroperoxide cytotoxicity by L-histidine.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1575
OP 1582
VO 275
IS 3
A1 A Guidarelli
A1 P Sestili
A1 A Cossarizza
A1 C Franceschi
A1 F Cattabeni
A1 O Cantoni
YR 1995
UL http://jpet.aspetjournals.org/content/275/3/1575.abstract
AB L-Histidine markedly increases inorganic and organic hydroperoxide-induced cytotoxicity and DNA single-strand breaks (SSBs) in Chinese hamster ovary cells. These effects were prevented by the iron chelator o-phenanthroline and were insensitive to the antioxidant N,N'-diphenyl-1,4-phenylenediamine. An excess of L-glutamine, a competitive inhibitor of L-histidine uptake, prevented the L-histidine-mediated enhancement of cytotoxicity induced by both inorganic and organic peroxides. L-Glutamine did not affect the level of DNA SSBs produced by H2O2/L-histidine, although it abolished the enhancement of SSB formation triggered by L-histidine in cells exposed to the organic peroxides. DNA SSBs generated by the organic hydroperoxides either alone or associated with L-histidine were removed with superimposable kinetics, whereas those produced by H2O2 in the presence of the amino acid were repaired more slowly than SSBs produced by the oxidant alone. DNA double-strand breaks, which are considered to be highly cytotoxic, were detected only in cells treated with H2O2 and L-histidine. Finally, L-histidine was shown to markedly increase the extent of mitochondrial damage produced by organic but not by inorganic hydroperoxides.