4- Nitropyrene

Nitropyrene Extracts of diesel exhaust gases were applied to [32]... 

Nitroindole 418 Nitrophenyl isocyanate reagent 77 1-Nitropyrene 61 N-Nitrosamines 107... 

Koizumi A, N Saitoh, T Suzuki, S Kamiyama (1994) A novel compound, 9-hydroxy-l-nitiopyrene, is a major photodegraded compound of 1-nitropyrene in the environment. Arch Environ Health 49 87-92. 

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... 

Nitro polycyclic aromatic hydrocarbons are environmental contaminants which have been detected in airborne particulates, coal fly ash, diesel emission and carbon black photocopier toners. These compounds are metabolized Tn vitro to genotoxic agents through ring oxidation and/or nitroreduction. The details of these metabolic pathways are considered using 4-nitrobiphenyl, 1- and 2-nitronaphthalene, 5-nitro-acenaphthene, 7-nitrobenz[a]anthracene, 6-nitro-chrysene, 1-nitropyrene, 1,3-, 1,6- and 1,8-dinitro-pyrene, and 1-, 3- and 6-nitrobenzo[a] pyrene as examples ... 

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. 

Although 1-aminopyrene is a reduced metabolite of 1-nitropyrene, this arylamine will not covalently bind to DNA in vitro (72). In contrast, when incubations were conducted with the intermediate reduction product, N-hydroxy-l-aminopyrene, extensive covalent binding to DNA was detected (72). This observation is consistent with the previous report that several N-hydroxy arylamines formed DNA adducts and induced mutations in S. typhimurium (116), and suggests that, at least for 1-nitropyrene, reduction to N-hydroxy-l-aminopyrene is a critical step in mutation induction. 

Other bacteria. Intestinal bacteria may play a critical role in the metabolic activation of certain nitroaromatic compounds in animals (119) and several reports have appeared on the metabolism of nitro PAHs by rat and human intestinal contents and microflora (120-123). Kinouchi et al. (120) found that 1-nitropyrene was reduced to 1-aminopyrene when incubated with human feces or anaerobic bacteria. More recently, Kinouchi and Ohnishi (121) isolated four nitroreductases from one of these anaerobic bacteria (Bacteroides fragilis). Each nitroreductase was capable of converting 1-nitropyrene into 1-aminopyrene, and one form catalyzed the formation of a reactive intermediate capable of binding DNA. Howard ej al. (116) confirmed the reduction of 1-nitropyrene to 1-aminopyrene by both mixed and purified cultures of intestinal bacteria. Two additional metabolites were also detected, one of which appeared to be 1-hydroxypyrene. Recently, similar experiments have demonstrated the rapid reduction of 6-nitro-BaP to 6-amino-BaP (123). 

Nitropyrene. 1-Nitropyrene is the principal nitro PAH found in diesel exhaust (40) and, therefore, has been the subject of intense study. Nachtman and Wei (133) found that under anaerobic conditions, 1-nitropyrene was reduced by hepatic S9, cytosol or microsomes to principally 1-aminopyrene. Only limited reduction occurred in the absence of cofactors, while maximum metabolism was observed in the presence of both FMN and NADPH. Although the microsomal fraction had the greatest specific activity toward 1-nitropyrene metabolism, the cytosol had 30 times the total activity. 

Saito et al. (134) found that the cytosolic nitroreductase activity was due to DT-diaphorase, aldehyde oxidase, xanthine oxidase plus other unidentified nitroreductases. As anticipated, the microsomal reduction of 1-nitropyrene was inhibited by 0 and stimulated by FMN which was attributed to this cofactor acting as an electron shuttle between NADPH-cytochrome P-450 reductase and cytochrome P-450. Carbon monoxide and type II cytochrome P-450 inhibitors decreased the rate of nitroreduction which was consistent with the involvement of cytochrome P-450. Induction of cytochromes P-450 increased rates of 1-aminopyrene formation and nitroreduction was demonstrated in a reconstituted cytochrome P-450 system, with isozyme P-448-IId catalyzing the reduction most efficiently. 

Bond (135) found that S9 preparations from rat nasal tissue have twice the specific activity for the oxidative metabolism of 1-nitropyrene as liver S9 and 10 times the activity of lung S9. Each S9 preparation gave similar metabolic profiles with the... 

In the PO-CL system, the compounds showing native fluorescence or that fluoresce after chemical derivatization can be detected. As examples of the PO-CL detection of native fluorescence compounds, dipyridamole and benzydamine in rat plasma [57] and fluphenazine [58] have been reported in the former method, the detection limits of dipyridamole and benzydamine were 345 pM and 147 nM in plasma, respectively. Diamino- and aminopyrenes were sensitively determined using TCPO and their detection limits were in the sub-fmol range [59], Carcinogenic compounds such as 1- nitropyrene and its metabolites, can also be determined by the HPLC-PO-CL system. Nonfluorescent nitropyrenes were converted into the corresponding fluorescent aminopyrenes by online reduction on a Zn column followed by detection 2-50-fmol detection limits were achieved in the determination of ethanol extracts from airborne particulates (Fig. 13) [60],... 

Figure 13 Chromatogram of an airborne particulate sample. Peaks 1 = 1,6-dinitropyr-ene 2 = 1,8-dinitropyrene 3 = 1,3-dinitropyrene 4 = 2-fluoro-7-nitrofluorene 5 = 1-nitropyrene. (From Ref. 60.)...

Trichloroethylene Vinyl chloride CYP3A4 Acetaminophen Aflatoxin Bi and Gi 6-Aminochrysene Benzo[a]pyrene 7,8-dihydrodiol Cyclophosphamide Ifosphamide 1-Nitropyrene Sterigmatocystin Senecionine... 

CYP3A4 acetaminophen aflatoxin Bj and Gj 6-aminochrysene henzo[n]pyrene 7,8-dihydrodiol cyclophosphamide Ifosphamide 1-Nitropyrene sterigmatocystin senecionine... 

Nitropolycyclic aromatic hydrocarbons have recently been identified in various foods. In smoked sausages, 1-nitropyrene, 2-nitronaphthalene, and 2-nitro-fluorene have been found in concentrations of about 4.2, 8.4, and 19.6 ng per g, respectively this is comparable with the levels found in roasted coffee beans (2.4, 4.0, and 30.1 ng per g). 

Nitropyrene also formed when pyrene deposited on glass filter paper containing sodium nitrite was irradiated with UV light at room temperature (Ohe, 1984). This compound was reported to have formed from the reaction of pyrene with NOx in urban air from St. Louis, MO (Randahl et al., 1982). Behymer and Hites (1985) determined the effect of different substrates on the rate of photooxidation of pyrene using a rotary photoreactor. The photolytic half-lives of pyrene using silica gel, alumina, and fly ash were 21,31, and 46 h, respectively. 

---