Early Oxidative DNA Damages and Late Development of Lung Cancer in Diesel Exhaust-Exposed Rats

Iwai, Kazuro; Adachi, Shuichi; Takahashi, Mihoko; Möller, Lennart; Udagawa, Tadashi; Mizuno, Satoru; Sugawara, Isamu

doi:10.1006/enrs.2000.4072

Cited by 79 publications

(41 citation statements)

References 27 publications

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“…In rat and mouse lungs, exposure to DEP through inhalation or intratracheal instillation causes oxidative DNA damage [Nagashima et al, 1995;Iwai et al, 2000] and DNA adduct formation [Gallagher et al, 1994;Sato et al, 2003]. Prolonged inhalation exposure results in respiratory tract tumors in rats [Mauderly et al, 1987;Nikula et al, 1995;Iwai et al, 1997;Valberg et al, 1999].…”

Section: Introductionmentioning

confidence: 98%

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Hashimoto

Amanuma

Hiyoshi

et al. 2007

Environ and Mol Mutagen

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Diesel exhaust (DE) is a major airborne pollutant of urban areas. It contains various polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs. In this study, gpt delta mice were treated with inhalation of 1 or 3 mg m(-3) DE, or a single intratracheal instillation of diesel exhaust particles (DEP) or DEP extract. In the lungs of mice treated with inhalation of 3 mg m(-3) DE for 12 weeks, the mutant frequency (MF) was 3.2-fold higher than that of the control group (1.90 x 10(-5) and 0.59 x 10(-5), respectively). An instillation of DEP and DEP extract resulted in a significant dose-dependent linear increase in MF. In mice treated with 0.5 mg DEP and 0.2 mg DEP extract, the MFs were 3.0- and 2.7-fold higher than that of the control group, respectively. The mutagenic potency (MF mg(-1)) of DEP extract (5.6 x 10(-5)) was double that of DEP (2.7 x 10(-5)), suggesting that the mutagenicity of the latter is derived primarily from compounds in the extract, which itself is responsible for ca. 50% of the weight of DEP. G:C-->A:T transitions were the predominant gpt mutation induced by all three treatments and G:C-->T:A transversions were induced by DEP and DEP extract. Guanine bases centered in nucleotide sequences such as GGA, TGA, CGG, and CGT were the major mutation targets of all three treatments. Thus, our results suggest that the mutagens contained in DEP such as PAH and nitrated PAHs induce mutations and may be responsible for carcinogenesis caused by inhalation of DE.

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Section: Introductionmentioning

confidence: 98%

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Hashimoto

Amanuma

Hiyoshi

et al. 2007

Environ and Mol Mutagen

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“…Exposure to diesel exhaust particles (DEP) of > 2 mg/m 3 has been documented in underground mines, railroad, construction, and in auto repair industries (1). Such exposures have been associated with pulmonary inflammation, fibrosis, lung cancer, increased rate of respiratory infections, and enhanced allergic sensitization (2)(3)(4)(5)(6). DEP are a complex mixture of polycyclic aromatic hydrocarbons (PAHs), ash, transition metals, and a carbon core.…”

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confidence: 99%

Alteration of intracellular cysteine and glutathione levels in alveolar macrophages and lymphocytes by diesel exhaust particle exposure.

Al-Humadi

Siegel

Lewis

et al. 2002

Environ Health Perspect

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Diesel engine exhaust is an occupational and environmental health concern. The particulate phase of diesel engine exhaust is thought to contribute to the increased prevalence of acute and chronic airway diseases. Exposure to diesel exhaust particles (DEP) of > 2 mg/m 3 has been documented in underground mines, railroad, construction, and in auto repair industries (1). Such exposures have been associated with pulmonary inflammation, fibrosis, lung cancer, increased rate of respiratory infections, and enhanced allergic sensitization (2-6). DEP are a complex mixture of polycyclic aromatic hydrocarbons (PAHs), ash, transition metals, and a carbon core. Major PAH components of DEP include phenanthrenes, fluorenes, naphthalenes, fluoranthrenes, and pyrenes (7). Previously we demonstrated that both the organic and the particulate components play a major role in DEP-induced pulmonary toxicity. Although the particulate induces acute inflammatory responses, the organic component suppresses both secretion of proinflammatory cytokines by alveolar macrophages (AM) and cell-mediated immunity in response to bacterial infection (4-6). In addition, DEP exposure has been linked to increased IgE production (3) and isotype switching in B cells to produce IgE in humans (8) and in animals (9). These studies suggest that DEP may suppress cellular but enhance allergic immune responses.Glutathione (GSH), long known for its protective function against oxidative cell damage (10), is thought to play a regulatory role in various lymphocyte functions. Depletion of intracellular GSH by buthionine sulfoximine decreases the proportion of CD8 + cells, inhibits the generation of large blastlike CD8 + cells, and decreases cytotoxic T-lymphocyte activity (11). The biosynthesis of GSH in lymphocytes requires intracellular cysteine (CYSH), an acid-soluble thiol produced and released by AM. Gmunder et al. (12) reported that exogenously added CYSH increases the intracellular GSH level and the activity of DNA synthesis in mitogen-stimulated lymphocytes, suggesting that CYSH also plays a regulatory role in mediating immunologically relevant functions of lymphocytes. Gmunder and Droge (11) demonstrated that GSH mediates cytokinedependent DNA synthesis in T lymphocytes and that the depletion of intracellular GSH inhibits relevant DNA synthesis and alters T-lymphocyte activity.Studies show that lymphocytes exhibit strong membrane transport activity for CYSH, but only a weak transport activity for cystine (13). In contrast, AM have a strong capacity for cystine uptake and the conversion of cystine into CYSH (14). In fact, Gmunder et al. (12) have shown that macrophages, when stimulated, function as a CYSH pump that takes up cystine and releases CYSH, increasing the intracellular GSH level of activated lymphocytes in the vicinity. These studies suggest that AM may regulate T-lymphocyte responses through thiol regulation. To provide more insight into the effects of DEP exposure on pulmonary immune responses, AM and pulmonary lymph node cells (LNC) from sali...

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“…Increasing awareness of the health impacts of diesel engine particulate matter (PM) emissions [1,2] has led to stringent legislation limiting the engine-out quantities of PM emitted from automotive sources. Increasing fuel injection pressure [3] and optimal use of exhaust gas recirculation [4] (among other combustion controls) can significantly reduce the engine-out PM.…”

Section: Introductionmentioning

confidence: 99%

Correcting mass measurement of diesel particulate filters at non-ambient temperatures

Williams

Garner

2009

Proceedings of the Institution of Mechanical Engineers, Part D:

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• This is an article from the journal, Proceedings of the In- Abstract: Diesel particulate filters (DPFs) are becoming a widespread method for reducing the particulate matter (PM) emissions from both on-highway and off-highway automotive diesel engines. Mass measurements of DPFs are commonly used to determine rapidly both the amount of PM trapped by the filter and the amount regenerated (removed) by regeneration systems. To avoid issues with adsorption of atmospheric water the filters are often weighed at elevated temperatures. It is shown in this work that at elevated temperatures the filters weigh less than at lower temperatures as a direct result of the buoyant hot air within the filter substrate. This study shows that consideration of the buoyancy forces allows for correction of the mass measurement for the errors relating to the non-ambient temperature of the filter, allowing mass measurements at elevated temperatures while avoiding adsorption of atmospheric water on to the filter substrate and, therefore, improving the accuracy of mass-measurement-based studies of filtration and regeneration performance of DPFs. It is demonstrated that a filter with approximately 85 per cent overall porosity weighed at 150 uC in ambient temperatures will have an error of about 0.3 g/l (typically about 10 per cent of the trapped PM mass) in the mass measurement when not correcting for the temperature. By way of an example, this is shown to have potentially an important effect on the calculated trapped PM.

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Early Oxidative DNA Damages and Late Development of Lung Cancer in Diesel Exhaust-Exposed Rats

Cited by 79 publications

References 27 publications

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust

Alteration of intracellular cysteine and glutathione levels in alveolar macrophages and lymphocytes by diesel exhaust particle exposure.

Correcting mass measurement of diesel particulate filters at non-ambient temperatures

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