Nitro-benzo pyrene

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). 

PAHs, polycyclic aromatic hydrocarbons DMBA, dimethylbenzanthracene BaP, benzo[ ]pyrene DEN, diethylnitrosamine MAMAc, methylazoxymethanol acetate MNNG, JV-methyl-JV -nitro-JV-nitrosogua-nidine TCE, trichloroethylene. 

In a solution containing oxygen, photolysis yields a mixture of 6,12-, 1,6-, and 3,6-diones. Nitration by nitrogen dioxide forms 6-nitro-, 1-nitro-, and 3-nitrobenzo[a]pyrene. When benzo [a] pyrene in methanol (1 g/L) was irradiated at 254 nm in a quartz flask for 1 h, the solution turned pale yellow. After 2 h, the solution turned yellow and back to clear after 4 h of irradiation. After 4 h, 99.67% of benzo[a]pyrene was converted to polar compounds. One of these compounds was identified as a methoxylated benzo[a]pyrene (Lu et al, 1977). A carbon dioxide yield of 26.5% was achieved when benzo [a] pyrene adsorbed on silica gel was irradiated with light (A, >290 nm) for 17 h (Freitag et al, 1985). 

FIGURE 10.12 Absorption spectra in methanol of benzo[a]pyrene and its 1-, 3-, and 6-nitro derivatives (adapted from Pitts et al., 1978). 

Subsequently, Ioki (1977) used ESR spectroscopy to confirm the production of the benzo[a]pyrene-6-oxyl radical in the nitro-nitrite photorearrangement of 6-NOz-BaP irradiated in benzene solution ... 

Although there are preliminary data supporting the antitumoral activity of quercetin, the most common flavonoid, in humans in the course of a Phase I clinical trial [189], direct evidence of the anticancer effect of flavonoids is derived almost exclusively from studies performed in animal models as well as studies performed on cultured cell lines, Fig. (2). Most animal studies on gastrointestinal cancer have focused on colon cancer using the azoxymethane (AOM) model in rats or mice [190-197]. There are also available reports on models of cancer of the stomach (induced by benzo[a]pyrene [198] or N-methyl-N-nitro-N-nitro so guanidine [199]), oesophagus (N-methyl-N-amylnitrosamine [200]), and the tongue/oral cavity (methyl-(acetoxymethyl)-nitrosamine [198], 7,12-dimethyl-... 

M.Y. Wang et al., Microsomal metabolism of 3-nitrobenzo[a]pyrene Effect of the nitro substituent on the regioselective metabolism of benzo[a]pyrene. J. Chinese Biochem. Soc. 

Epoxidation and hydroxylation A-Dealkylation O-Dealkylation -Dealkylation -Oxidation A-Oxidation P-Oxidation Desulfuration Dehalogenation Nitro reduction Azo reduction Cytochrome P450 (CYP) Aflatoxin, aldrin, benzo[a]pyrene, bromobenzene, naphthalene Ethylmorphine, atrazine, dimethylnitrocarbamate, dimethylaniline p-Nitroanisole, chlorfenvinphos, codeine Methylmercaptan Thiobenzamide, phorate, endosulfan, methiocarb, chlorpromazine 2-Acetylaminofluorene Diethylphenylphosphine Parathion, fonofos, carbon disulfide CCLt, CllCb Nitrobenzene O-Aminoazotoluene Flavin-Containing Monooxygenase (FMO)... 

This method was first applied to relative electron affinities of substituted nitro-benzenes. All but one of these has been measured by HPMS TCT studies. However, the Ea of s-butyl nitrobenzene has only been determined by collisional ionization and is still listed in the NIST tables as 2.17(20) eV. This value is referenced to a high value for nitrobenzene and should be about 1 eV lower [60]. The electron affinities of aromatic hydrocarbons have been reported using the collisional ionization method. The value for biphenylene is larger than that obtained from half-wave reduction potentials. The values for pyrene, anthracene, and c-CgHg are consistent with other reported values, but the values for benzanthracene, coronene, and benzo[ghi]perylene are significantly lower than the largest precise value and are attributed to excited states. 

The antimutagenic effects of ajoene were investigated by the Ames test. Ajoene inhibited mutagenesis induced by both benzo[a]pyrene (B[a]P) and 4-nitro-l,2-phenylenediamine (NPD) in a dose-dependent manner. In particular, NPD-induced mutagenesis was more effectively suppressed by ajoene than the B[a]P-induced type. Furthermore, the inhibition of mutagenesis by ajoene was more effective for transition-type mutations than for the frame shift type. HPLC analysis of B[a]P metabolism in the presence of the rat liver microsomal fraction (S-9) showed that ajoene dose-dependently inhibited the metabolic activation of B[a]P which suggests that ajoene affected the metabolic enzymes in the S-9 fraction [100]. 

Benzene itself is quite toxic to humans and can cause severe liver damage toluene, although not harmless. Is much less toxic. How can such different behavior of two very similar compounds be possible To eliminate benzene from the body, the aromatic ring must be oxidized, but intermediates in this oxidation are damaging. However, the methyl side chain of toluene can be oxidized to give benzoic acid, which can be excreted. None of the intermediates in this process causes health problems. Conversely, nitro-substituted PAHs, especially of benzo[a]pyrene, are often about 1 0 times more carcinogenic than their unsubstituted analogues, and studies are currently underway to understand this effect. 

More recently, freshly isolated diploid Syrian hamster embryo cells were used in a quantitative focus assay. Transformed foci, observed within 3 weeks on a monolayer of normal cells, were induced in secondary cultures of cells after treatment of mass cultures for 6 days with A -acetoxy-2-acetylamino-fluorene, aflatoxin Bi, benzo [a]pyrene, jS-propriolactone, dibenz [a,/i] anthracene, ethyl methanesulfonate, 3-methylcholanthrene, methyl methanesulfo-nate, or A -methyl-A -nitro-A -nitrosoguanidine. 

Polycyclic aromatic hydrocarbons are ubiquitous in the atmosphere. Maximum concentrations often occur in urban areas, resulting primarily from engine exhaust and other forms of combustion. These processes produce compoimds that may be carried across continents and oceans, particularly in highly industrialized areas of the northern hemisphere (Simoneit and Mazurek, 1981). High molecular weight PAH, such as fluoranthene, pyrene, chrysene, benz[a]anthracene, benzofluoranthenes, benzo[a]pyrene, and benzo[e]pyrene are commonly encountered in urban atmospheres (Simoneit and Mazurek, 1981). Low molecular weight PAH are also widely distributed and include unsubstituted and alkyl naphathalene, phenanthrene, acenaphthene, and fluorene. PAH react in the upper atmosphere with NO to form nitro-derivatives, which are mutagenic. 

---