1-Nitropyrene mutagenicity

Table 9 Inhibitory Effects of Polygonum cuspidatum Crude Extracts and Emodin on 1-nitropyrene Mutagenicity with Salmonella typhimurium TA98...

Reduction of nitroarenes has been demonstrated in species of Clostridium and Eubacte-rium, and was associated with the reduction in the mutagenic activity of 1-nitropyrene, and... 

Compared to the extensive data that have been obtained on the mutagenicity of nitro PAHs in S. typhimurium, relatively little is known about the metabolism of these compounds in this organism. Messier et al. (67) reported that incubation of 1-nitropyrene with S. typhimurium TA98 yielded 1-aminopyrene and 1-acetylaminopyrene as major and minor metabolites, respectively. The reduction of 1-nitropyrene was slow and was accompanied by a slow formation of DNA adducts. When incubations were conducted with the nitroreductase-deficient strain, TA100 F50, both the extent of 1-amino-pyrene formation and DNA binding decreased. Howard ej al. (71,115) also found reduction of 1-nitropyrene to 1-aminopyrene in strains TA98, TA1538 and ATCC 14028. 

Kinouchi T, Nishifuji K, Tsutsui H, et al. 1988. Mutagenicity and nitropyrene concentration of indoor air particulates exhausted from a kerosene heater. Jpn J Cancer Res 79(1) 32-41. 

DC056 Tang, X., and R. Edenharder. Inhibitions of mutagenicity of 2-nitro-fluorene, 3-nitrofluaranthene and 1 -nitropyrene by vitamins, porphyrins and related compounds, and vegetable and fruit juices and solvent extract. 

Some of these N-, O-, and S-atom-functionalized polycyclic aromatic compounds (PACs) are powerful bacterial mutagens and animal, and possible human, carcinogens, e.g., the exocyclic nitro-substituted PAH 1-nitropyrene, VI, which is a primary pollutant in diesel exhaust (IARC, 1989). The endocyclic heterocyclic PAC dibcnz[fl,/ ]acridine, VII, is also classified as a possible human carcinogen (IARC, 1987 see Sections B and C). 

The variation in the mutagenic potency of the control compounds was similar to that of the environmental samples the exception was 1-nitropyrene, for which the reproducibility ranged from 127 to 132%. 

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... 

FIGURE 10.22 Direct mutagenicity of ambient particles (mutagen density, rev m-3, TA98, —S9) as a function of ambient concentrations of 2-nitropyrene, a directly mutagenic product of a gas-phase atmospheric reaction initiated by OH radical attack on pyrene. Samples collected at six sites in California with different types of emissions ( ) Glendora (O) Yuba City ( ) Concord ( ) Mammoth Lakes ( a ) Oildale ( ) Reseda (see Fig. 10.22) (adapted from Atkinson et al., 1988a). 

The generality of this reaction of N02 with particle-associated PAHs was demonstrated when, under similar laboratory conditions, perylene (a weak promutagen) was converted to 3-nitroperylene, and pyrene (a nonmutagen), at a slower rate, to 1-nitropyrene both nitro-PAHs are direct-acting frameshift mutagens. In a similar experiment, chrysene was not nitrated this is consistent with its low reactivity in the Nielsen reactivity scale (Table 10.30). 

Subsequently, Benson (1985) reported 1-nitropyrene deposited on glass photodecomposed in sunlight with a half-life of 14 h. The reaction was accompanied by loss of the nitro group, formation of a phenolic derivative and possibly quinones, and a significant reduction in mutagenicity, consistent with the Chapman mechanism and previous results on nitro-BaP isomers (Finlayson-Pitts and Pitts, 1986). 

Stark and co-workers (1985) reported that irradiation of a 0.1 mM solution of 1-nitropyrene in 2-propanol with light from 320 to 418 nm changes its absorption spectrum and concurrently results in almost total loss of its direct ( —S9) or activatable ( + S9) mutagen activity in the Ames Salmonella assay. 

A similar concomitant loss of mutagenicity with loss of compound was observed when Holloway and coworkers (1987) irradiated (A > 310 nm) 1-nitropyrene,... 

Initially, major attention was focused on emissions of diesel soot from light- and heavy-duty motor vehicles, because the particle extracts contained such direct-acting bacterial mutagens and animal and possible human carcinogens (IARC Group 2B, 1989) as 1-nitropyrene (1-N02-PY) and the 1,6- and 1,8-dinitropyrenes (DNP), as well as a third isomer, 1,3-dinitropyrene, IARC Group III. For example, Paputa-Peck and coworkers (Paputa-Peck et al., 1983 IARC, 1989) reported 100 nitro-PAHs (17 positively identified) in... 

Arey, J., B. Zielinska, W. P. Harger, R. Atkinson, and A. M. Winer, The Contribution of Nitrofluoranthenes and Nitropyrenes to the Mutagenic Activity of Ambient Particulate Organic Matter Collected in Southern California, Mutat. Res., 207, 45-51 (1988b). 

Kinouchi, T., K. Nishifuji, H. Tsutsui, S. L. Hoare, and Y. Ohnishi, Mutagenicity and Nitropyrene Concentration of Indoor Air Particulates Exhausted from a Kerosene Heater, Jpn. J. Cancer Res. (Gann), 79, 32-41 (1988). 

Lewtas, J., L. King, K. Williams, L. Ball, and D. DeMarini, Bioassay-Directed Fractionation of 1-Nitropyrene Metabolites Generation of Mutagrams by Coupling Reverse-Phase HPLC with Microsuspension Mutagenicity Assays, Mutagenesis, 6, 481-489 (1990b). 

Pitts, J. N., Jr., D. M. Lokensgard, W. Harger, T. S. Fisher, V. Mejia, J. Schuler, G. M. Scorziell, and Y. A. Katzenstein, Mutagens in Diesel Exhaust Identification and Direct Activities of 6-Nitro-benzo[a]pyrene, 9-Nitroanthracene, f-Nitropyrene, and 5H-Phenanthro[4,5-bco ]pyran-5-one, Mutat. Res., 103, 24f-249 (1982a). 

Rosenkranz, H. S., Predicting the Carcinogenic Potential of Environmental Nitropyrenes, Environ. Mol. Mutagen., 10, 149-156 (1987). 

Stark, G., J. Stauff, H. G. Miltenburger, and I. Stumm-Fischer, Photodecomposition of 1-Nitropyrene and Other Direct-Acting Mutagens Extracted from Diesel-Exhaust Particulates, Mutat. Res., 155, 27-33 (1985). 

Heflich, R. H., Howard, P. C. Beland, F. A. (1985). 1-Nitrosopyrene An intermediate in the metabolic activation of 1-nitropyrene to a mutagen in Salmonella typhimurium TA1538. Mutation Research, 149, 25-32. 

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