Mutagenicity and genotoxicity of nitroarenes

Rosenkranz, Herbert S.; Mermelstein, Robert

doi:10.1016/0165-1110(83)90034-9

Cited by 568 publications

(103 citation statements)

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“…The general reduction of the mutagenic effects of the test compounds after addition of S9 mix suggests that phase I enzymes that are active in the enzyme mix do not contribute to the conversion of the nitro-compounds to DNA-reactive metabolites, and that the homogenate causes detoxification, which may be due to enzymatic reactions or direct binding to proteins or both. Similar observations were made with other energyproducing nitro-compounds [Lachance et al, 1999], and also with nitroaromatic drugs and environmental nitropyrenes [Rosenkranz and Mermelstein, 1983;IARC, 1984IARC, , 1989.…”

Section: Discussionsupporting

confidence: 74%

Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities

Grummt

Wunderlich

Chakraborty³

et al. 2006

Environ. Mol. Mutagen.

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2-Amino-4,6-dinitrobenzoic acid (2-A-4,6-DNBA), 4-amino-2,6-dinitrobenzoic acid (4-A-2,6-DNBA), 2,4,6-trinitrobenzoic acid (2,4,6-TNBA), 2-amino-4, 6-dinitrobenzylalcohol (2-A-4,6-DNBAlc), 4-amino-2,6-dinitrobenzylalcohol (4-A-2,6-DNBAlc), 2,4-dinitrotoluol-5-sulfonic acid (2,4-DNT-5-SA), 2,4-dinitrotoluol-3-sulfonic acid (2,4-DNT-3-SA), and 2, 4-dinitrobenzoic acid (2,4-DNBA) are derivatives of nitro-explosives that have been detected in groundwater close to munitions facilities. In the present study, the genotoxicity of these compounds was evaluated in Salmonella/microsome assays (in strains TA100 and TA98, with and without S9 and in TA98NR without S9), in chromosomal aberration (CA) tests with Chinese hamster fibroblasts (V79), and in micronucleus (MN) assays with human hepatoma (HepG2) cells. All compounds except the sulfonic acids were positive in the bacterial mutagenicity tests, with 2,4,6-TNBA producing the strongest response (8023 revertants/micromol in TA98 without S9 activation). 2-A-4,6-DNBA was a direct acting mutagen in TA98, but negative in TA100. The other positive compounds were approximately 1-3 orders of magnitude less mutagenic than 2,4,6-TNBA in TA98 and in TA100; relatively strong effects ( approximately 50-400 revertants/micromol) were produced by the benzylacohols in the two indicator strains. With the exception of 2,4-DNBA, the mutagenic responses were lower in the nitroreductase-deficient strain TA98NR than in the parental strain. 2,4-DNBA produced a marginally positive response in the V79-cell CA assay; the other substances were devoid of activity. Only the benzoic acids were tested for MN induction in HepG2 cells, and all produced positive responses. As in the bacterial assays, the strongest effect was seen with 2,4,6-TNBA (significant induction at >or=1.9 microM). 4-A-2,6-DNBA was positive at 432 microM; the weakest effect was observed with 2,4,-DNBA (positive at >or=920 microM). The differences in the sensitivity of the indicator cells to these agents can be explained by differences in the activities of enzymes involved in the activation of the compounds. The strong responses produced by some of the compounds in the human-derived cells suggest that environmental exposure to these breakdown products of nitro-explosives may pose a cancer risk in man.

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Section: Discussionsupporting

confidence: 74%

Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities

Grummt

Wunderlich

Chakraborty³

et al. 2006

Environ. Mol. Mutagen.

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“…1), and characterized the purified mutant enzyme (Tables I, II, and III). TA98NR is a strain deficient in the nitroreductase and was isolated as a mutant resistant to the killing effects of nitrofuran (14,35). The purified mutant protein, in which leucine 33 is replaced with arginine (L33R), showed no detectable level of nitrofurazone nitroreductase activity under the standard assay conditions.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, S. typhimurium TA98NR, a nitroreductase-deficient strain, is resistant to both the killing and mutagenic effects of nitroarenes, whereas S. typhimurium YG1021, a nitroreductase-overproducing strain, is extremely sensitive to the effects (14,15). The latter strain was constructed in this laboratory by introducing a multicopy number plasmid carrying the gene encoding the nitroreductase of S. typhimurium into an Ames tester strain TA98 (16).…”

mentioning

confidence: 99%

Purification and Characterization of Wild-type and Mutant “Classical” Nitroreductases of Salmonella typhimurium

Watanabe

Nishino

Takio

et al. 1998

Journal of Biological Chemistry

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"Classical" nitroreductase of Salmonella typhimurium is a flavoprotein that catalyzes the reduction of nitroaromatics to metabolites that are toxic, mutagenic, or carcinogenic. This enzyme represents a new class of flavin-dependent enzymes, which includes nitroreductases of Enterobacter cloacae and Escherichia coli, flavin oxidoreductase of Vibrio fischeri, and NADH oxidase of Thermus thermophilus. To investigate the structurefunction relation of this class of enzymes, the gene encoding a mutant nitroreductase was cloned from S. typhimurium strain TA1538NR, and the enzymatic properties were compared with those of the wild-type. DNA sequence analysis revealed a T to G mutation in the mutant nitroreductase gene, predicting a replacement of leucine 33 with arginine. In contrast to the wild-type enzyme, the purified protein with a mutation of leucine 33 to arginine has no detectable nitroreductase activities in the standard assay conditions and easily lost FMN by dialysis or ultrafiltration. In the presence of an excess amount of FMN, however, the mutant protein exhibited a weak but measurable enzyme activity, and the substrate specificity was similar to that of the wildtype enzyme. Possible mechanisms by which the mutation greatly diminishes binding of FMN to the nitroreductase are discussed.

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“…14 As shown in Table IV, the selectivity for dinitrobenzene isomers on Sil-AN n were less than that on Sil-CN. It seems to be reasonable because dinitrobenzenes are so small that the molecular-shape selectivity derived from the polymer effect of poly(acrylonitrile) are not demonstrated.…”

Section: Selectivity For Dinitrobenzene and Dinitrotoluenementioning

confidence: 90%

Polymer Effect on Molecular Recognition. Enhancement of Molecular-Shape Selectivity for Polycyclic Aromatic Hydrocarbons by Poly(acrylonitrile)

Takafuji

Dong

Goto

et al. 2002

Polym J

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ABSTRACT:Poly(acrylonitrile) immobilized onto porous silica (Sil-AN n ) was prepared to evaluate the effect of polymerization degree of poly(acrylonitrile) on selective interaction with polycyclic aromatic hydrocarbons. The HPLC using the packed column (Sil-AN n ) and an aqueous solution as a mobile phase showed higher selectivity for structural isomers of polycyclic aromatic hydrocarbons compared with simply cyanopropylated silica (Sil-CN) and alkylated silica (Sil-C 4 ). It was considered that silica-supported poly(acrylonitrile) recognized molecular aromaticity of π-electron containing compounds rather than molecular hydrophobicity. Furthermore, similar results were obtained in the selectivity towards geometrical isomers such as trans-and cis-stilbenes or triphenylene and o-terphenyl and structural isomers such as o-, m-, p-terphenyls. Also the separation factors increased with an increase in polymerization degree of AN n . This paper discusses that polymeric structures enhance the selectivity.KEY WORDS Polymer Grafting Silica / High Performance Liquid Chromatography (HPLC) / Multiple π-π Interactions / CN-π-to-benzene-π Interaction / Molecular Aromaticity / Geometrical Isomers / Structural Isomers / Specific behaviors of many polymers are based on their configurations and conformations. The chemical structures of monomer units and their arrangements influence on the conformational structures of polymer chain and then closely relate to their functions whose are carried out by multiple interactions through accumulation of their functional groups. In biological systems, there are many examples of protein polymers, the structures of which determine the biological functions. The molecular assemblies such as bio-membranes also show specific behaviors in bio-systems.On the other hand, synthetic polymers are used as many industrial materials such as films, fibers and adhesions. It is well-known that crystallinity and polymerization degree influence the properties of polymers. Many researchers have reported physical and chemical properties of polymers with functional groups in their main and side chains because it is important to mimic the functions of biopolymers using simply synthetic polymers. This will expand possible applications of polymers.We have investigated the hybridization between silica gels and polymers 1-10 such as polystyrene, 1 poly(acrylonitrile), 6 and poly(methyl acrylate) 3 which were applied to separation. These polymers possess π-electrons to be used as a π-π interaction source and thus have been applied as packing materials for liquid chromatography with π-electron recognition. As a re- † To whom correspondence should be addressed. sult, we have found that the polymer-immobilized silica showed much better selectivity for structural isomers of polycyclic aromatic hydrocarbons than the corresponding monomer-immobilized silica. In this paper, we wish to report the effects of polymerization degree of polymers on separation behavior of polycyclic aromatic hydrocarbons by using poly(acrylonitrile). ...

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Mutagenicity and genotoxicity of nitroarenes

Cited by 568 publications

References 118 publications

Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities

Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities

Purification and Characterization of Wild-type and Mutant “Classical” Nitroreductases of Salmonella typhimurium

Polymer Effect on Molecular Recognition. Enhancement of Molecular-Shape Selectivity for Polycyclic Aromatic Hydrocarbons by Poly(acrylonitrile)

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