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Title: Purified rat liver DT-diaphorase potentiates the mutagenicity of 1,3-, 1,6- and 1,8-dinitropyrene

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:5863333
;  [1]
  1. Louisiana State Univ., Baton Rouge (United States)

The effect of highly purified rat liver cytosolic DT-diaphorase on the mutagenicity of 1,3-, 1,6- and 1,8-dinitropyrene (DNP) was studied in the Ames Salmonella typhimurium mutagenicity assay. DT-diaphorase over the range of 0 - 0.78 {mu}g/plate increased the mutagenicity of all three DNP in S. typhimurium TA 98 to a maximum of 3-fold. In the nitroreductase-deficient strain, TA98NR, 1,6- and 1,8-DNP were activated to a lesser extent in the presence of equal amounts of DT-diaphorase as compared to TA98. The mutagenicity of 1,3-DNP was markedly lowered in TA98NR and DT-diaphorase did not increase the mutagenicity of this toxicant except at the highest level utilized. DT-diaphorase was found to activate 1,6-, but not 1,3-DNP to mutagenic intermediates in TA98 18DNP{sub 6}, a strain deficient in O-acetyltransferase activity. The results suggest that DT-diaphorase not only catalyzes reduction of the parent DNP but also that of partially reduced metabolites generated from that DNP. This may result in increased formation of the penultimate mutagenic species. Thus, while DT-diaphorase is commonly viewed as having antimutagenic properties with certain compounds the opposite appears to be true for DNP.

OSTI ID:
5863333
Report Number(s):
CONF-9104107-; CODEN: FAJOE
Journal Information:
FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
Country of Publication:
United States
Language:
English