Metabolism of 7,12-dimethylbenz[a]anthracene in mouse skin homogenates analyzed with high-pressure liquid chromatography

J. DiGiovanni, Thomas J Slaga, D. L. Berry, M. R. Juchau

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Abstract

The metabolism of 7, 12-dimethylbenz[a]anthracene (DMBA) in epidermal homogenates from 3-methylcholanthrene-pretreated mice was analyzed with high-pressure liquid chromatography. Metabolism was undetectable in the absence of pretreatment. Specific activities in epidermal homogenates from pretreated mice were found to be approximately 100 to 1000 times lower than those observed in comparable incubations containing hepatic microsomes from MC-pretreated rats. The major metabolite formed was identified as 7-hydroxymethyl-12-methylbenz[a]anthracene. Each of the known hydroxymethyl metabolites also was present in detectable quantities. The K-region diol was not measurably present in incubations with mouse skin homogenates or rat liver microsomes from MC-pretreated animals. 7,8-Benzoflavone, 5,6-benzoflavone, and 17-β-estradiol were found to be potent inhibitors of the metabolic transformation of DMBA by epidermal homogenates in vitro, whereas butylated hydroxytoluene and 1,1,1-trichloro-2,3-propene oxide had little effect on or enhanced metabolite formation from DMBA in vitro.

Original languageEnglish (US)
Pages (from-to)295-301
Number of pages7
JournalDrug Metabolism and Disposition
Volume5
Issue number3
StatePublished - 1977
Externally publishedYes

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High pressure liquid chromatography
9,10-Dimethyl-1,2-benzanthracene
Metabolites
Metabolism
Skin
High Pressure Liquid Chromatography
Rats
beta-Naphthoflavone
Butylated Hydroxytoluene
Methylcholanthrene
Liver Microsomes
Microsomes
Liver
Estradiol
Animals
anthracene
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Metabolism of 7,12-dimethylbenz[a]anthracene in mouse skin homogenates analyzed with high-pressure liquid chromatography. / DiGiovanni, J.; Slaga, Thomas J; Berry, D. L.; Juchau, M. R.

In: Drug Metabolism and Disposition, Vol. 5, No. 3, 1977, p. 295-301.

Research output: Contribution to journalArticle

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abstract = "The metabolism of 7, 12-dimethylbenz[a]anthracene (DMBA) in epidermal homogenates from 3-methylcholanthrene-pretreated mice was analyzed with high-pressure liquid chromatography. Metabolism was undetectable in the absence of pretreatment. Specific activities in epidermal homogenates from pretreated mice were found to be approximately 100 to 1000 times lower than those observed in comparable incubations containing hepatic microsomes from MC-pretreated rats. The major metabolite formed was identified as 7-hydroxymethyl-12-methylbenz[a]anthracene. Each of the known hydroxymethyl metabolites also was present in detectable quantities. The K-region diol was not measurably present in incubations with mouse skin homogenates or rat liver microsomes from MC-pretreated animals. 7,8-Benzoflavone, 5,6-benzoflavone, and 17-β-estradiol were found to be potent inhibitors of the metabolic transformation of DMBA by epidermal homogenates in vitro, whereas butylated hydroxytoluene and 1,1,1-trichloro-2,3-propene oxide had little effect on or enhanced metabolite formation from DMBA in vitro.",
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AU - Juchau, M. R.

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N2 - The metabolism of 7, 12-dimethylbenz[a]anthracene (DMBA) in epidermal homogenates from 3-methylcholanthrene-pretreated mice was analyzed with high-pressure liquid chromatography. Metabolism was undetectable in the absence of pretreatment. Specific activities in epidermal homogenates from pretreated mice were found to be approximately 100 to 1000 times lower than those observed in comparable incubations containing hepatic microsomes from MC-pretreated rats. The major metabolite formed was identified as 7-hydroxymethyl-12-methylbenz[a]anthracene. Each of the known hydroxymethyl metabolites also was present in detectable quantities. The K-region diol was not measurably present in incubations with mouse skin homogenates or rat liver microsomes from MC-pretreated animals. 7,8-Benzoflavone, 5,6-benzoflavone, and 17-β-estradiol were found to be potent inhibitors of the metabolic transformation of DMBA by epidermal homogenates in vitro, whereas butylated hydroxytoluene and 1,1,1-trichloro-2,3-propene oxide had little effect on or enhanced metabolite formation from DMBA in vitro.

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