Original Contributions8-Hydroxyguanosine formed in human lung tissues and the association with diesel exhaust particles
Introduction
It has been reported by many investigators that cellular DNA damage occurrs due to oxygen free radicals generated in ionizing radiation, environmental mutagens and carcinogens, and may be involved in mutagenesis, carcinogenesis and the aging process [1], [2], [3]. The C-8 position of deoxyguanosine residue in DNA produces 8-hydroxyguanosine (8-OHdG), one of the most critical lesions generated from deoxyguanosine in DNA by oxygen radicals [4], [5], [6]. Determination of 8-OHdG in humans has been investigated by many researchers, in studies on polymorphonuclear leukocytes [7], peripheral lymphocytes [8], peripheral lung tissues [9], and breast tissues with breast cancer [10]. However, it has also been reported that fullerene C60, as carbon vapor produced by laser irradiation of graphite, also generated singlet oxigen, and 8-OHdG was formed in an in vitro system by lipid peroxidation [11].
Diesel exhaust particles were mutagenic for Salmonella typhimurium and mammalian cell cultures, and carcinogenic in animal experiments [12]. In addition to cigarette smoke, the large increase in lung cancer incidence was thought to involve diesel exhaust particles, and it has been reported that a significant correlation between air pollution and lung cancer was epidemiologically observed [13]. Major mutagenic and carcinogenic components in the particles have been demonstrated on the basis of analysis of their biological and chemical properties [12]. In these components, nitrated polycyclic aromatic compounds (NO2-PAH), substantial mutagens and carcinogens were deposited in human lung tissues by inhaling environmental air pollutants even if the deposited amounts of each compound were at low levels [14], [15]. 8-OHdG formation causing oxidative damage has already been reported as causing pulmonary injury due to diesel exhaust particles (DEPs) [16], and motorcycle exhaust particles [17], and the DEP toxicity was found to be due to production of superoxide (O2•−) and a hyroxyl radical (•OH).
The present study aimed to evaluate 8-OHdG detected by administration of DEPs in mice, and moreover, to demonstrate whether or not carboneceous particles in diesel exhaust particles may be involved in the process of oxidative damage in test done in vivo using mice.
Section snippets
Chemicals
1-Nitropyrene (1-NP) and 1,8-dinitropyrene (1,8-DNP) were prepared as described previously [14], and benzo[a]pyrene (B[a]P) was purchased from Aldrich (Milwaukee, WI, USA). Catalase, super oxide dismutase (SOD), and deferoxamine mesylate were obtained from Sigma Chemical Co. (St Louis, MO, USA).
Lung specimens
Lung specimens with carcinoma (80 cases) were surgically resected as reported previously [14], and bioassayed for mutagenicity. The ages of the patients ranged from 10 to 85 years. Lung specimens
Mutagenicity of extracts of lung tissues for salmonella strain YG3003
Lung tissues (81 cases) resected from patients with carcinoma were treated with β-glucuronidase, and extracted with dichloromethane as described in Materials and Methods. Mutagenic activity of the lung tissue extracts indicated an increase with age, though it was not statistically significant (Fig. 1). The strain YG3003 used in this study was a mutant that was sensitive to active oxygen. Therefore, it was suggested that the extracts from lung tissue induced oxidative damage in the DNA residue
Discussion
It has been suggested that DEPs may be associated with human lung carcinogenesis. The extracts of DEPs were obviously mutagenic for Salmonella strains and mammalian cell cultures, and also carcinogenic in rats and mice [12]. These mutagenic and carcinogenic agents were mostly composed of various chemicals such as polycyclic aromatic hydrocarbons and their nitrated derivatives. Similarly, the extracts from DEPs were found to be mutagenic for Salmonella strains YG3003 originating from TA102, a
References (26)
- et al.
A comparison of the 8-hydrodeoxyguanosine, chromosome aberrations and micronucleus techniques for the assessment of the genotoxicity of mercury compounds in human blood lymphocytes
Mutation Res.
(1996) - et al.
Analysis of environmental carcinogens associated with the incidence of lung cancer
Toxicol. Lett.
(1998) - et al.
Involvement of oxidative stress in motorcycle exhaust particle-induced DNA damage and inhibition of intercellular communication
Mutation Res.
(1998) - et al.
Construction of mutants of Salmonella typhimurium deficient in 8-hydroxyguanine DNA glycosylase and their sensitivities to oxidative mutagens and nitro compounds
Mutation Res.
(1997) - et al.
8-Hydroxyguanosine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions
J. Biol. Chem.
(1992) - et al.
Biological effects of diesel exhaust particles. I. In vitro production of superoxide and in vivo toxicity in mouse
Free Radic. Biol. Med.
(1993) - et al.
Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG
Nature
(1991) - et al.
Major alterations in the nucleotide structure of DNA in cancer of the female breast
Cancer Res.
(1991) - et al.
Tumor progression and oxidant-antioxidant status
Carcinogenesis
(1996) - et al.
Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair
Carcinogenesis
(1986)