Free radical formation in isolated murine keratinocytes treated with organic peroxides and its modulation by antioxidants.
Electron paramagnetic resonance spin-trapping has been used to study the production of free radicals from tert-butyl hydroperoxide, tert-butyl peroxybenzoate, cumene hydroperoxide and ethyl hydroperoxide in isolated murine keratinocytes. Free radical species could be trapped from keratinocytes treated with all peroxides, with radicals produced from both one-electron oxidative and reductive pathways. The hindered phenolic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), which are known to inhibit peroxide-induced tumour promotion in vivo, decreased the amount of radical adduct production at a concentration of 10 mM, with BHA being significantly more effective than BHT. That all the peroxides in this study produced free radicals in keratinocytes, and that BHA and BHT decreased the amounts of radicals trapped, suggests that free radical production by organic peroxide compounds is involved in their in vivo tumour-promoting activity.
Timmins
G S
GS
Department of Chemistry, University of York, UK.
Davies
M J
MJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002083:Butylated Hydroxyanisole / Q000494:pharmacology / Q000627:therapeutic use; D002084:Butylated Hydroxytoluene / Q000494:pharmacology / Q000627:therapeutic use; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism* / Q000633:toxicity; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D010545:Peroxides / Q000378:metabolism* / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D013113:Spin Labels; D020122:tert-Butylhydroperoxide
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D016166:Free Radical Scavengers; D005609:Free Radicals; D010545:Peroxides; D013113:Spin Labels; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; D020122:tert-Butylhydroperoxide