Microbial metabolism and detoxification of 7,12-dimethylbenz[a]anthracene

David C McMillan, Peter P. Fu, James P. Freeman, Dwight W. Miller, Carl E. Cerniglia

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Six strains of fungi grown on Sabouraud dextrose broth in the presence of 7,12-dimethylbenz[a]anthracene (DMBA) were surveyed for their ability to metabolize DMBA. Experiments with [14C]DMBA indicated that the extent of formation of organic-soluble metabolites ranged from 6 to 28% after 5 days of incubation, depending on the organism tested. The yields of water-soluble metabolites also varied, and ranged from 1 to 33% after 5 days. Cunninghamella elegans ATCC 36112 and Syncephalastrum racemosum UT-70 exhibited the highest DMBA-metabolizing activity among the organisms surveyed. S. racemosum metabolized DMBA primarily to 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA)_ and 7,12-dihydroxymethylbenz[a]anthracene (7,12-diOHMBA). Minor metabolites included 7-OHM-12-MBA-trans-5,6-, 8,9- and 10,11-dihydrodiols, and glucuronide and sulfate conjugates of phenolic derivatives of DMBA. In contrast, the major DMBA metabolites produced by C. elegans were water-soluble. The predominant organic-soluble metabolites produced by C. elegans included 7-OHM-12-MBA-trans-5,6-, 8,9- and 10,11-dihydrodiols. DMBA-trans-3,4-dihydrodiol was also detected. Circular dichroism spectral analysis revealed that the major enantiomer of the 7-OHM-12-MBA-trans-8,9-dihydrodiol formed by each organism has an S,S absolute configuration, while the major enantiomers of the 5,6-, 10,11- and 3,4-dihydrodiols had an R,R configuration. The mutagenic activity of extracts from S. racemosum exposed to DMBA were determined in Salmonella typhimurium TA98. The mutagenicity of DMBA decreased by 36% over a period of 5 days as 33% of the compound was metabolized. Comparison of these results with previously reported results in mammalian systems suggests that there are similarities and differences between the fungal and mammalian oxidation of DMBA and that the overall balance of fungal metabolism is towards a detoxification rather than a bioactivation pathway.

Original languageEnglish (US)
Pages (from-to)211-225
Number of pages15
JournalJournal of Industrial Microbiology
Volume3
Issue number4
DOIs
StatePublished - Jun 1 1988

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9,10-Dimethyl-1,2-benzanthracene
Detoxification
Anthracene
Metabolites
Metabolism
Enantiomers
Dextrose
Salmonella
Dichroism
Fungi
Spectrum analysis
Water
anthracene
Cunninghamella
Derivatives
Oxidation
Glucuronides
Salmonella typhimurium
Circular Dichroism
Sulfates

Keywords

  • 7,12-Dimethylbenz[a]anthracene
  • Cunninghamella elegans
  • Fungi
  • Microbial metabolism
  • Syncephalastrum racemosum

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology

Cite this

Microbial metabolism and detoxification of 7,12-dimethylbenz[a]anthracene. / McMillan, David C; Fu, Peter P.; Freeman, James P.; Miller, Dwight W.; Cerniglia, Carl E.

In: Journal of Industrial Microbiology, Vol. 3, No. 4, 01.06.1988, p. 211-225.

Research output: Contribution to journalArticle

McMillan, David C ; Fu, Peter P. ; Freeman, James P. ; Miller, Dwight W. ; Cerniglia, Carl E. / Microbial metabolism and detoxification of 7,12-dimethylbenz[a]anthracene. In: Journal of Industrial Microbiology. 1988 ; Vol. 3, No. 4. pp. 211-225.
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