TY - JOUR
T1 - Evidence for dissimilar mechanisms of enhancement of inorganic and organic hydroperoxide cytotoxicity by L-histidine
AU - Guidarelli, A.
AU - Sestili, P.
AU - Cossarizza, A.
AU - Franceschi, C.
AU - Cattabeni, F.
AU - Cantoni, O.
PY - 1995
Y1 - 1995
N2 - 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.
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.
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M3 - Article
C2 - 8531131
AN - SCOPUS:0029554995
VL - 275
SP - 1575
EP - 1582
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 3
ER -