Evidence for dissimilar mechanisms of enhancement of inorganic and organic hydroperoxide cytotoxicity by L-histidine

A. Guidarelli, P. Sestili, A. Cossarizza, C. Franceschi, F. Cattabeni, O. Cantoni

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1575-1582
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume275
Issue number3
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Pharmacology

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