DNA Adducts and Carcinogenicity of Nitro-Polycyclic Aromatic Hydrocarbons

Abstract

We have been interested in the structure-activity relationships of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs), and have focused on the correlation of structural and electronic features with biological activities, including mutagenicity and tumorigenicity. In our studies, we have emphasized 1-, 2-, 3-, and 6-nitrobenzo 177-184 (1994)

Comparison of the nucleic acid covalent binding capacity of two nitro-substituted benzazolo[3,2-a]quinolinium salts upon enzymatic reduction

“…The ability of XO to reductively activate multiple substrates is documented (Bunting et al, 1980), including the covalent binding of nitroarenes via HX/XO (Fu et al, 1994, Ritter et al, 2002. In the present study, the reaction of NBQ-38 with the highest concentration of HX resulted in the highest level of adduct formation.…”

PAHs and PCBs accumulated by SPMD-based virtual organisms and feral fish in Three Gorges Reservoir, China

“…Many of the PAHs are known to be carcinogenic and mutagenic compounds (Mastral et al, 2003). Further transition or metabolism can lead to the formation of even more toxic compounds like nitrated PAHs of which some are suspected to have higher mutagenicity than their precursors (Fu et al, 1994;Topinka et al, 1998). Polychlorinated biphenyls (PCBs) are mixtures of chlorinated hydrocarbons which were widely used in the 1950s and 60s as dielectric fluids in transformers and capacitors, heat transfer and hydraulic fluids, and as plasticizers in paints, flame retardants, pesticide extenders, and adhesives (US EPA, 2003).…”

Molecular characterization of mutation and comparison of mutation profiles in thehprt gene of Chinese hamster ovary cells treated with benzo[a]pyrenetrans-7,8-diol-anti-9,10-epoxide, 1-nitrobenzo[a]pyrenetrans-7,8-diol-anti-9,10-epoxide, and 3-nitrobenzo[a]pyrenetrans-7,8-diol-anti-9,10-epoxide

“…It is known that covalent binding of BaP-DE to DNA results in 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9, IO-tetrahydrobenzo[a]pyrene (dG-BaP-DE) as the predominant adduct, along with several minor adducts [Dipple et al, 1984;Osborne and Crosby, 19871 [Fu et al, , 1994. These adducts have also been detected from the metabolism of 1-and 3-nitro-BaP-DE by rat liver microsomes in the presence of calf thymus DNA [Fu et al, 1993, unpublished data].…”

“…Aerobic metabolism, in general, produces epoxides, trans-dihydrodiols, phenols, and quinones as the predominant metabolites [Fu, 19901. Because most of the nitroPAHs so far studied are derived from nontumorigenic PAHs, ring-oxidation typically results in detoxification [Fu, 19901. We have been interested in the structure-Abbreviations: CHO, Chinese hamster ovary; BaF, benzo [a]pyrene; nitroBaP, nitrobenzo [a]pyrene; BaF-DE, trans-7,8-dihydroxy-anti-9,lO-epoxy-7,8,9,1O-teb-ahydrobenzo[a]pyrene; anti-9,10epoxy-7,8,9,1O-tetrahydro-l -nitrobenzo [a]pyrene; 3-nitro-BaF-DE, rrans-7,8-dihydroxy-anti-9,1 O-epoxy-7,8,9,1 O-tetrahydro-3-nitrobenzo[a]-pyrene; dG-BaF-DE, lO-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,1O-tetrahydrobenzo[a]pyrene; dG-l-nitro-BaP-DE, 10-(deoxyguanosin-N2-yl)- 7,8,9-trihydroxy-7,8,9, 10-tetmhydro-l-nitrobenm[a]pyrene; dG-3-nitro-BaP-DE, 1O-(deoxyguanosin-NZ-yl)-7,8,9-trihydroxy-7,8,9,1O-tetrahydro-3-nitrobenzo[a]pyrene; hprf, hypoxanthine-guanine phosphoribosyltransferase (gene); PCR, polymerase chain reaction; FBS, fetal bovine serum; DMSO, activity relationships of nitro-PAHs [Beland et al, 1985;Fu, 1990;Fu et al, 1986Fu et al, , 1988aFu et al, ,b, 1993Fu et al, , 1994Chou et al, 1984Chou et al, , 1985Chou et al, , 1986Wang et al, 1988;Jung et al, 1991;Yu et al, 1992;HerrenoSaenz et al, 19921, with a particular focus on the isomeric nitrobenzo [a]pyrenes (nitro-BaPs) that are derived from benzo [a]pyrene (BaP), the prototype for the study of PAH carcinogenesis [Yang and Silverman, 1988;Dipple et al, 1984;Osborne and Crosby, 19871. Both 1 -nitro-BaP and 3-nitro-BaP are environmental contaminants and are potent mutagens in Salmonella typhimurium TA98 in the presence and absence of rat liver S9 activation; they are also moderate mutagens in Chinese hamster ovary (CHO) cells with S9 activation [Chou et al, 1984[Chou et al, , 1985Pitts et al, 1978Pitts et al, , 1984…”