1,2-Dihydro-1,2-dihydroxy-5-methylchrysene, a Major Activated Metabolite of the Environmental Carcinogen 5-Methylchrysene

Stephen S. Hecht, Edmond LaVoie, RÜbert Mazzarese, Shantu Amin, Victoria Bedenko

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurlum. Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I. Each peak was collected and tested for mutagenicity with activation. Significant mutagenic activity was observed primarily in Peak E and to a lesser extent in Peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (Peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hy-droxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.

Original languageEnglish (US)
Pages (from-to)2191-2194
Number of pages4
JournalCancer Research
Volume38
Issue number7
StatePublished - Jul 1 1978

Fingerprint

Environmental Carcinogens
Aroclors
5-methylchrysene
1,2-dihydro-1,2-dihydroxy-5-methylchrysene
Mutagens
Salmonella
High Pressure Liquid Chromatography
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hecht, Stephen S. ; LaVoie, Edmond ; Mazzarese, RÜbert ; Amin, Shantu ; Bedenko, Victoria. / 1,2-Dihydro-1,2-dihydroxy-5-methylchrysene, a Major Activated Metabolite of the Environmental Carcinogen 5-Methylchrysene. In: Cancer Research. 1978 ; Vol. 38, No. 7. pp. 2191-2194.
@article{e3cfa59aec0f49acbac5f625123783be,
title = "1,2-Dihydro-1,2-dihydroxy-5-methylchrysene, a Major Activated Metabolite of the Environmental Carcinogen 5-Methylchrysene",
abstract = "The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurlum. Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I. Each peak was collected and tested for mutagenicity with activation. Significant mutagenic activity was observed primarily in Peak E and to a lesser extent in Peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (Peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0{\%} from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6{\%} from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hy-droxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.",
author = "Hecht, {Stephen S.} and Edmond LaVoie and R{\"U}bert Mazzarese and Shantu Amin and Victoria Bedenko",
year = "1978",
month = "7",
day = "1",
language = "English (US)",
volume = "38",
pages = "2191--2194",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

1,2-Dihydro-1,2-dihydroxy-5-methylchrysene, a Major Activated Metabolite of the Environmental Carcinogen 5-Methylchrysene. / Hecht, Stephen S.; LaVoie, Edmond; Mazzarese, RÜbert; Amin, Shantu; Bedenko, Victoria.

In: Cancer Research, Vol. 38, No. 7, 01.07.1978, p. 2191-2194.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 1,2-Dihydro-1,2-dihydroxy-5-methylchrysene, a Major Activated Metabolite of the Environmental Carcinogen 5-Methylchrysene

AU - Hecht, Stephen S.

AU - LaVoie, Edmond

AU - Mazzarese, RÜbert

AU - Amin, Shantu

AU - Bedenko, Victoria

PY - 1978/7/1

Y1 - 1978/7/1

N2 - The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurlum. Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I. Each peak was collected and tested for mutagenicity with activation. Significant mutagenic activity was observed primarily in Peak E and to a lesser extent in Peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (Peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hy-droxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.

AB - The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurlum. Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I. Each peak was collected and tested for mutagenicity with activation. Significant mutagenic activity was observed primarily in Peak E and to a lesser extent in Peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (Peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hy-droxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.

UR - http://www.scopus.com/inward/record.url?scp=0018193958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018193958&partnerID=8YFLogxK

M3 - Article

C2 - 350385

AN - SCOPUS:0018193958

VL - 38

SP - 2191

EP - 2194

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 7

ER -