Metabolism of the antibacterial triclocarban by human epidermal keratinocytes to yield protein adducts.
Previous studies of triclocarban suggest that its biotransformation could yield reactive metabolites that form protein adducts. Since the skin is the major route of triclocarban exposure, present work examined this possibility in cultured human keratinocytes. The results provide evidence for considerable biotransformation and protein adduct formation when cytochrome P450 activity is induced in the cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a model Ah receptor ligand. Since detecting low adduct levels in cells and tissues is difficult, we utilized the novel approach of accelerator mass spectrometry for this purpose. Exploiting the sensitivity of the method, we demonstrated that a substantial portion of triclocarban forms adducts with keratinocyte protein under the P450 inducing conditions employed.
Institute of Food Toxicology and Chemical Analysis, University of Veterinary Medicine Hannover, Hannover 30173, Germany.
Nils Helge
NH
Schebb
Bruce A
BA
Buchholz
Bruce D
BD
Hammock
Robert H
RH
Rice
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D002224:Carbanilides / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002224:Carbanilides; D000072317:Polychlorinated Dibenzodioxins; D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; C009540:triclocarban