Dinitropyrenes, metabolic activation

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). 

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. 

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],... 

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