Free Radical Production During Metabolism of Organic Hydroperoxides by Normal Human Keratinocytes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1993-07

AUTHORS

A Iannone, A Marconi, G Zambruno, A Giannetti, V Vannini, A Tomasi

ABSTRACT

Evidence of a relationship between tumor production induced by various organic (hydro)peroxides and free radical formation has been shown in cultured murine keratinocytes and human skin-tumor cell line. In the present study the bioactivation of cumene hydroperoxide, t-butyl-hydroperoxide, and benzoyl peroxide via one-electron oxidation or reduction was compared in freshly isolated and in cultured normal human keratinocytes. The formation of methyl free radicals during the metabolism of cumene and t-butyl-hydroperoxide was shown by the electron spin resonance-spin trapping technique. Radical formation increased under hypoxic conditions. An intracellular activation site was demonstrated by the use of two spin-trapping agents, the hydrophilic, membrane-impermeable, 3,5-dibromo-4-nitrosobenzenesulfonic acid and the lipophilic, membrane-permeable alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone. At 30 min incubation and 25 mM concentration, hydroperoxides exhibited cytotoxicity, as indicated by trypan blue exclusion and lactate dehydrogenase release assay; free radicals were concurrently trapped. Hydroperoxides at a lower concentration (1 mM) did not significantly affect cell viability. However, free radical production was still detected using a membrane-permeable spin trap. The incubation of keratinocytes with benzoyl peroxide did not show any peroxide-dependent radical adduct. No significant differences in bioactivation capability were demonstrated between freshly isolated and cultured human keratinocytes. The results indicate that cultured human keratinocytes can be used as a model system for the study of the metabolic activation to free radical intermediates of toxic and carcinogenic compounds in the epidermis. More... »

PAGES

59-63

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1111/1523-1747.ep12359510

DOI

http://dx.doi.org/10.1111/1523-1747.ep12359510

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024485791

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8392529


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