Formation and tumorigenicity of benzo[b]fluoranthene metabolites in mouse epidermis

J. Edgar Geddie, Shantu Amin, Keith Huie, Stephen S. Hecht

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The metabolism in mouse epidermis of benzo[b]fluoranthene (BbF) was studied. [3H]BbF was applied topically, mice were killed at various intervals, and metabolites were extracted from the epidermis and analyzed by h.p.l.c The major metabolites were identified by comparisons to standards as 4-, 5-, and 6-hydroxyBbF. Sulfate and glucuronide conjugates of these hydroxyBbF were also detected. Minor metabolites included 12-hydroxyBbF, BbF-1,2-diol, and BbF-11,12-diol. BbF-9,10-diol, the only known tumorigenic oxygenated derivative of BbF, was not detected. The further metabolism of BbF-9,10-diol was studied in vitro, using rat liver 9000 g supernatant. The major metabolites were identified by their spectral characteristics as 5-and 6-hydroxyBbF-9,10-diol. Little if any BbF-9,10,11,12-tetraol was detected. 5-and 6-HydroxyBbF-9,10-diol were not detected as metabolites of [3H]BbF in mouse epidermis. Several known and potential BbF metabolites-BbF-1,2-diol, BbF-11,12-diol, BbF-9,10-diol, BbF-9,10-diol-11, 12-epoxide, 5-and 6-hydroxyBbF-9,10-diol, 1-hydroxyBbF, 5-hydroxyBbF, and 6-hydroxyBbF-were tested for tumor initiating activity on mouse skin. Among these, only BbF-9,10-diol showed high tumorigenic activity, but no evidence has been obtained for its formation in vivo from BbF. These studies do not support the hypothesis that BbF is metabolically activated through formation of the bay region diol epoxide, BbF-9,10-diol-11,12-epoxide.

Original languageEnglish (US)
Pages (from-to)1579-1584
Number of pages6
JournalCarcinogenesis
Volume8
Issue number11
DOIs
StatePublished - Nov 1 1987

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Epidermis
Epoxy Compounds
Glucuronides
Sulfates
Skin
benzo(b)fluoranthene
Liver
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Geddie, J. Edgar ; Amin, Shantu ; Huie, Keith ; Hecht, Stephen S. / Formation and tumorigenicity of benzo[b]fluoranthene metabolites in mouse epidermis. In: Carcinogenesis. 1987 ; Vol. 8, No. 11. pp. 1579-1584.
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abstract = "The metabolism in mouse epidermis of benzo[b]fluoranthene (BbF) was studied. [3H]BbF was applied topically, mice were killed at various intervals, and metabolites were extracted from the epidermis and analyzed by h.p.l.c The major metabolites were identified by comparisons to standards as 4-, 5-, and 6-hydroxyBbF. Sulfate and glucuronide conjugates of these hydroxyBbF were also detected. Minor metabolites included 12-hydroxyBbF, BbF-1,2-diol, and BbF-11,12-diol. BbF-9,10-diol, the only known tumorigenic oxygenated derivative of BbF, was not detected. The further metabolism of BbF-9,10-diol was studied in vitro, using rat liver 9000 g supernatant. The major metabolites were identified by their spectral characteristics as 5-and 6-hydroxyBbF-9,10-diol. Little if any BbF-9,10,11,12-tetraol was detected. 5-and 6-HydroxyBbF-9,10-diol were not detected as metabolites of [3H]BbF in mouse epidermis. Several known and potential BbF metabolites-BbF-1,2-diol, BbF-11,12-diol, BbF-9,10-diol, BbF-9,10-diol-11, 12-epoxide, 5-and 6-hydroxyBbF-9,10-diol, 1-hydroxyBbF, 5-hydroxyBbF, and 6-hydroxyBbF-were tested for tumor initiating activity on mouse skin. Among these, only BbF-9,10-diol showed high tumorigenic activity, but no evidence has been obtained for its formation in vivo from BbF. These studies do not support the hypothesis that BbF is metabolically activated through formation of the bay region diol epoxide, BbF-9,10-diol-11,12-epoxide.",
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Formation and tumorigenicity of benzo[b]fluoranthene metabolites in mouse epidermis. / Geddie, J. Edgar; Amin, Shantu; Huie, Keith; Hecht, Stephen S.

In: Carcinogenesis, Vol. 8, No. 11, 01.11.1987, p. 1579-1584.

Research output: Contribution to journalArticle

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N2 - The metabolism in mouse epidermis of benzo[b]fluoranthene (BbF) was studied. [3H]BbF was applied topically, mice were killed at various intervals, and metabolites were extracted from the epidermis and analyzed by h.p.l.c The major metabolites were identified by comparisons to standards as 4-, 5-, and 6-hydroxyBbF. Sulfate and glucuronide conjugates of these hydroxyBbF were also detected. Minor metabolites included 12-hydroxyBbF, BbF-1,2-diol, and BbF-11,12-diol. BbF-9,10-diol, the only known tumorigenic oxygenated derivative of BbF, was not detected. The further metabolism of BbF-9,10-diol was studied in vitro, using rat liver 9000 g supernatant. The major metabolites were identified by their spectral characteristics as 5-and 6-hydroxyBbF-9,10-diol. Little if any BbF-9,10,11,12-tetraol was detected. 5-and 6-HydroxyBbF-9,10-diol were not detected as metabolites of [3H]BbF in mouse epidermis. Several known and potential BbF metabolites-BbF-1,2-diol, BbF-11,12-diol, BbF-9,10-diol, BbF-9,10-diol-11, 12-epoxide, 5-and 6-hydroxyBbF-9,10-diol, 1-hydroxyBbF, 5-hydroxyBbF, and 6-hydroxyBbF-were tested for tumor initiating activity on mouse skin. Among these, only BbF-9,10-diol showed high tumorigenic activity, but no evidence has been obtained for its formation in vivo from BbF. These studies do not support the hypothesis that BbF is metabolically activated through formation of the bay region diol epoxide, BbF-9,10-diol-11,12-epoxide.

AB - The metabolism in mouse epidermis of benzo[b]fluoranthene (BbF) was studied. [3H]BbF was applied topically, mice were killed at various intervals, and metabolites were extracted from the epidermis and analyzed by h.p.l.c The major metabolites were identified by comparisons to standards as 4-, 5-, and 6-hydroxyBbF. Sulfate and glucuronide conjugates of these hydroxyBbF were also detected. Minor metabolites included 12-hydroxyBbF, BbF-1,2-diol, and BbF-11,12-diol. BbF-9,10-diol, the only known tumorigenic oxygenated derivative of BbF, was not detected. The further metabolism of BbF-9,10-diol was studied in vitro, using rat liver 9000 g supernatant. The major metabolites were identified by their spectral characteristics as 5-and 6-hydroxyBbF-9,10-diol. Little if any BbF-9,10,11,12-tetraol was detected. 5-and 6-HydroxyBbF-9,10-diol were not detected as metabolites of [3H]BbF in mouse epidermis. Several known and potential BbF metabolites-BbF-1,2-diol, BbF-11,12-diol, BbF-9,10-diol, BbF-9,10-diol-11, 12-epoxide, 5-and 6-hydroxyBbF-9,10-diol, 1-hydroxyBbF, 5-hydroxyBbF, and 6-hydroxyBbF-were tested for tumor initiating activity on mouse skin. Among these, only BbF-9,10-diol showed high tumorigenic activity, but no evidence has been obtained for its formation in vivo from BbF. These studies do not support the hypothesis that BbF is metabolically activated through formation of the bay region diol epoxide, BbF-9,10-diol-11,12-epoxide.

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