Dinitropyrenes, metabolic

Recently, Bryant t al. (70) examined the metabolism of 1,8-dinitropyrene in several S. typhimurium strains and found reduction to l-amino-8-nitropyrene and 1,8-diaminopyrene. In addition, other unidentified metabolites were detected in strains which were sensitive to 1,8-dinitropyrene-induced mutations (TA98 and TA98NR) but not in the resistant strains, TA98/1,8-DNP and TA98NR/1,8-DNP6. 

The human cell mutagenicities of several mono- and dinitropyrenes were determined by Busby and coworkers (1994b) in a forward mutation assay using a metabolically competent line of MCL-5 cells. Minimum detectable mutagen concentrations (MMC, in nmol ml-1 the smaller the detectable concentration, the greater the potency) were as follows 1,6-dinitropyrene, 0.8 1,8-dinitropyrene, 1.5 4-nitropyrene, 3.1 1-nitro-pyrene, 9.1. Other PACs tested, 2-nitropyrene, 1,3-dinitropyrene, and pyrene, were nonmutagens in this... 

Busby, W. F., Jr., B. W. Penman, and C. L. Crespi, Human Cell Mutagenicity of Mono- and Dinitropyrenes in Metabolically Competent MCL-5 Cells, Mutat. Res., 322, 233-242 (1994b). 

E.K. Fifer et al., Synthesis and mutagenicity of l-nitro-6-nitrosopyrene and l-nitro-8-nitro-sopyrene, potential intermediates in the metabolic activation of 1, 6- and 1, 8-dinitropyrene. Carcinogenesis 7, 65-70 (1986)... 

N-hydroxy-Trp-P-2. More recently, the metabolism of IQ has been assessed by the same laboratory (Yamazoe et al., 1983). As was found for Trp-P-2, IQ is metabolized to the N-hydroxy derivative. A specific form of purified cytochrome P-450 designated P-448 Ila appears to be responsible for the metabolic activation of IQ. The activity of this N-hydroxy metabolite is calculated to be 5 X 10E5 revertants per nmole. This metabolite is the most mutagenic compound ever tested in the Ames/Salmonella assay, three times more potent than 1,8 dinitropyrene (Rosenkranz et al. 1980). 

Another outstanding aspect of Ephedra lays behind its antimutagenic activity. The extracts of in vitro culture of Ephedra were tested against benzo[a]pyrene, 1, 6-dinitropyrene and 3,9-dinitrofluoranthene and showed a remarkable inhibition against benzo[a]pyrene, whereas that inhibition against 1, 6-diNP and 3, 9-diNF was varied from 20 % to 86 %. Researchers concluded that the differences in inhibition might be due to inactivation of metabolic enzymes [12],... 

Kinouchi, T., and Y. Ohnishi. 1986. Metabolic activation of 1-nitropyrene and 1,6-dinitropyrene by nitroreductases from Bacteroides fragilis and distribution of nitroreductase activity in rats. Microbiol. Immunol. 30 979-992. 

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