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.
Free-Radical Production During Metabolism Of Organic Hydroperoxides By Normal Human Keratinocytes / Iannone, Anna; Marconi, Alessandra; G., Zambruno; Giannetti, Alberto; V., Vannini; Tomasi, Aldo. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - STAMPA. - 101(1993), pp. 59-63.
Data di pubblicazione: | 1993 |
Titolo: | Free-Radical Production During Metabolism Of Organic Hydroperoxides By Normal Human Keratinocytes |
Autore/i: | Iannone, Anna; Marconi, Alessandra; G., Zambruno; Giannetti, Alberto; V., Vannini; Tomasi, Aldo |
Autore/i UNIMORE: | |
Rivista: | |
Volume: | 101 |
Pagina iniziale: | 59 |
Pagina finale: | 63 |
Codice identificativo ISI: | WOS:A1993LM65300011 |
Codice identificativo Scopus: | 2-s2.0-0027176596 |
Codice identificativo Pubmed: | 8392529 |
Citazione: | Free-Radical Production During Metabolism Of Organic Hydroperoxides By Normal Human Keratinocytes / Iannone, Anna; Marconi, Alessandra; G., Zambruno; Giannetti, Alberto; V., Vannini; Tomasi, Aldo. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - STAMPA. - 101(1993), pp. 59-63. |
Tipologia | Articolo su rivista |
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