Mutagenicity and Carcinogenicity of Nitroarenes and Their Sources in the Environment

Abstract

Nitroarenes are postulated to play a principal part among mutagens/carcinogens which are induced in the combustion process and, in addition, are widely distributed in the environment. This review deals with the following points concerning nitroarene toxicity. Data on the mutagenicity of nitroarenes obtained by short-term bioassays are expected to provide us with sufficient information for us to determine their genotoxicity and carcinogenicity. Therefore, mutagenicity detected with Salmonella, Escherichia, and yeast test systems is discussed. Genotoxicity in mammalian cells is also important for determining the mutagenic properties of nitroarenes. In this article, mutagenicity in Chinese hamster ovary cells, sister chromatid exchanges, and cell transformation is summarized. The metabolism of nitroarenes in vivo and in vitro is of importance for determining their behavior and active forms. Therefore, current studies regarding metabolism of nitroarenes are described. Carcinogenicity of nitroarenes for animals has been reported by many workers. In this review, the incidence and histological features of tumors induced by nitroarenes are described. Furthermore, the possible association between human lung cancer and nitroarenes is discussed. Sources of nitroarenes in the environment are given. The results of various chemical tests for identifying nitroarenes are summarized, and speculation on the risk of nitroarenes for humans is presented.

Occurrence, behavior and removal of typical substituted and parent polycyclic aromatic hydrocarbons in a biological wastewater treatment plant

“…Though PAHs originated from incomplete combustion and vehicle emission (Manoli and Samara, 1999), the contribution of direct atmospheric deposition to the rivers was only 7% . In recent years, some typical substituted PAHs (SPAHs), including methyl PAHs (MPAHs), oxygenated PAHs (OPAHs) and nitrated PAHs (NPAHs) have been paid much attention due to their higher toxicities than PAHs, such as carcinogenicity, mutagenicity and allergic diseases (Tokiwa et al, 1986;Durant et al, 1996). Besides the similar sources to PAHs, NPAHs and OPAHs can also be formed from PAHs by photo-chemical oxidation in atmosphere with NO x , O 3 and OH (Bamford and Baker, 2003;Wang et al, 2007;Kojima et al, 2010), and OPAHs from biological transformation in soil with white rot fungi (Lundstedt et al, 2007;Haritash and Kaushik, 2009), respectively.…”

Role of Intestinal Microflora in Metabolism of Glutathione Conjugates of 1-Nitropyrene 4,5-Oxide and 1-Nitropyrene 9,10-Oxide.

“…1-NP can be transformed into active derivatives through various pathways, which are either reduction of vitro group to N-hydroxy-l-NP, ring oxidation or combination of nitroreduction and ring oxidation (Tokiwa and Ohnishi 1986). A DNA adduct indicative of reductive metabolism, N-(deoxyguanosin-8-yl)-1-aminopyrene (dG-C8-AP), has been identified to be a minor adduct in vivo, and additional major DNA adducts have been observed (Roy et al 1989).…”

“…1-Nitropyrene (1-NP), one of the nitrated polycyclic aromatic hydrocarbons, is a major environmental pollutant and has been shown to be mutagenic for bacteria and cultured mammalian cells and also tumorigenic in the experimental animals (Tokiwa and Ohnishi 1986). 1-NP can be transformed into active derivatives through various pathways, which are either reduction of vitro group to N-hydroxy-l-NP, ring oxidation or combination of nitroreduction and ring oxidation (Tokiwa and Ohnishi 1986).…”

The treatment of Chagas disease patients with nitroderivative is unsatisfactory

“…In contrast, malignant neoplasia was neither seen in the T. cruzi-infected rabbits nor in uninfected, control rabbits. The etiology of chemically induced cancer may involve the covalent binding of the carcinogen to DNA (adducts) leading to mutation in oncogenes or tumor suppressor genes, and ultimately to tumors 17,30,44,45,47 . These formed adducts have the potential to bind covalently to DNA and induce oxidative damage to DNA.…”

“…Severe cytotoxicity has been described for several nitroderivatives, and, in recent decades, these compounds have been shown to possess a variable degree of mutagenic, teratogenic, carcinogenic and sterilizing activities 4,5,16,17,27,30,37,44,45,47 . Cytotoxicity and genotoxicity associated with nitroderivatives seem to depend on the binding of electrophilic radicals to macromolecules and DNA, after enzymatic reduction of the nitro-group and generation of free electrophilic radicals, such as nitro-anions, hydroxyl, singlet oxygen and hydrogen peroxide 18,21,30,31,41 .…”