Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 230-234 |
| Number of pages | 5 |
| Journal | Journal of Biochemical and Molecular Toxicology |
| Volume | 26 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2012 |
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Keywords
- Accelerator mass spectrometry
- Biotransformation
- Cytochrome P450
- Keratinocytes
- Protein adducts
- Reactive metabolites
- TCDD
- Triclocarban
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Molecular Medicine
- Toxicology
- Health, Toxicology and Mutagenesis
Cite this
Metabolism of the antibacterial triclocarban by human epidermal keratinocytes to yield protein adducts. / Schebb, Nils Helge; Buchholz, Bruce A.; Hammock, Bruce D.; Rice, Robert H.
In: Journal of Biochemical and Molecular Toxicology, Vol. 26, No. 6, 06.2012, p. 230-234.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metabolism of the antibacterial triclocarban by human epidermal keratinocytes to yield protein adducts
AU - Schebb, Nils Helge
AU - Buchholz, Bruce A.
AU - Hammock, Bruce D.
AU - Rice, Robert H.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Accelerator mass spectrometry
KW - Biotransformation
KW - Cytochrome P450
KW - Keratinocytes
KW - Protein adducts
KW - Reactive metabolites
KW - TCDD
KW - Triclocarban
UR - http://www.scopus.com/inward/record.url?scp=84862671862&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862671862&partnerID=8YFLogxK
U2 - 10.1002/jbt.21411
DO - 10.1002/jbt.21411
M3 - Article
C2 - 22711420
AN - SCOPUS:84862671862
VL - 26
SP - 230
EP - 234
JO - Journal of Biochemical and Molecular Toxicology
JF - Journal of Biochemical and Molecular Toxicology
SN - 1095-6670
IS - 6
ER -