New experimental data linking secondhand smoke exposure to lung cancer in nonsmokers

Kim, Sangin; Yoon, Jae-In; Tommasi, Stefania; Besaratinia, Ahmad

doi:10.1096/fj.11-199984

Cited by 19 publications

(36 citation statements)

References 34 publications

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“…7 E, F and 8 C ). The above‐specified mutational signatures of these 3 carcinogens are comparable to those found previously in the same model system using the conventional low‐throughput method (62, 70, 71).…”

Section: Development Of a High‐throughput Next‐generation Sequencing‐supporting

confidence: 81%

Genotoxicity of tobacco smoke‐derived aromatic amines and bladder cancer: current state of knowledge and future research directions

Besaratinia

Tommasi

2013

FASEB j.

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Bladder cancer is a significant public health problem, worldwide. In the United States, bladder cancer is the fourth most common cancer in men, and its recurrence rate is the highest among all malignancies. Tobacco smoking is the leading risk factor for bladder cancer. The risk of bladder cancer is directly related to the intensity and duration of smoking, while quitting smoking reduces this risk. The increased risk of smokers for developing bladder cancer is attributable to their exposure to aromatic amines, which constitute a family of known bladder carcinogens present in tobacco smoke. The underlying mechanism of action of aromatic amines in the genesis of bladder cancer is not, however, fully delineated. Research has identified a genotoxic mode of action, specifically DNA adduction and mutagenicity, for aromatic amines, which may account for their carcinogenicity. The present review summarizes our current knowledge on the DNA adduction and mutagenicity of aromatic amines in relation to smoking-associated bladder cancer. For illustrative purposes, representative results from published research on aromatic amine-induced DNA adduction and mutagenesis are discussed. The direction of future research on the underlying mechanisms of tobacco smoke-associated bladder carcinogenesis is also outlined. Understanding the molecular mechanisms of bladder carcinogenesis is essential for improving future strategies for prevention, early detection, treatment, and prognosis of this malignancy.

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Section: Development Of a High‐throughput Next‐generation Sequencing‐supporting

confidence: 81%

Genotoxicity of tobacco smoke‐derived aromatic amines and bladder cancer: current state of knowledge and future research directions

Besaratinia

Tommasi

2013

FASEB j.

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“…In vivo treatment of Big Blue® mice with 4-ABP, a known bladder carcinogen with moderate mutagenic potency (13), resulted in a 9.9-fold increase in background cII mutant frequency from 2.09 ± 0.20 × 10 − 5 in bladder DNA of control (solvent-treated) mice to 20.62 ± 4.77 × 10 − 5 in bladder DNA of 4-ABP-treated mice ( P = 0.0079). In vivo exposure of Big Blue® mice to SHS, a known pulmonary carcinogen with comparatively weak mutagenic potency (12), resulted in a 2.1-fold increase in background cII mutant frequency from 2.00 ± 0.29 × 10 − 5 in lung DNA of control (clean-air-treated) mice to 4.09 ± 0.79 × 10 − 5 in lung DNA of SHS-treated mice ( P = 0.0011).…”

Section: Resultsmentioning

confidence: 99%

“…However, the mutation detection systems employed in these studies may not necessarily represent some of the key determinants of mutagenesis in mammalian cells, for example, chromatin structure, DNA sequence contexts, fidelity and efficiency of DNA polymerases and DNA repair (4,35–38). In addition, these systems are not suitable for investigating organ-specific mutagenicity in relation to tumorigenesis, which is a unique property of certain carcinogens (12,13). The latter is reflective of the need for studying target-organ mutagenesis in animal models of tumorigenicity.…”

Section: Discussionmentioning

confidence: 99%

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A high-throughput next-generation sequencing-based method for detecting the mutational fingerprint of carcinogens

Besaratinia

Yoon

et al. 2012

Nucleic Acids Research

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Many carcinogens leave a unique mutational fingerprint in the human genome. These mutational fingerprints manifest as specific types of mutations often clustering at certain genomic loci in tumor genomes from carcinogen-exposed individuals. To develop a high-throughput method for detecting the mutational fingerprint of carcinogens, we have devised a cost-, time- and labor-effective strategy, in which the widely used transgenic Big Blue® mouse mutation detection assay is made compatible with the Roche/454 Genome Sequencer FLX Titanium next-generation sequencing technology. As proof of principle, we have used this novel method to establish the mutational fingerprints of three prominent carcinogens with varying mutagenic potencies, including sunlight ultraviolet radiation, 4-aminobiphenyl and secondhand smoke that are known to be strong, moderate and weak mutagens, respectively. For verification purposes, we have compared the mutational fingerprints of these carcinogens obtained by our newly developed method with those obtained by parallel analyses using the conventional low-throughput approach, that is, standard mutation detection assay followed by direct DNA sequencing using a capillary DNA sequencer. We demonstrate that this high-throughput next-generation sequencing-based method is highly specific and sensitive to detect the mutational fingerprints of the tested carcinogens. The method is reproducible, and its accuracy is comparable with that of the currently available low-throughput method. In conclusion, this novel method has the potential to move the field of carcinogenesis forward by allowing high-throughput analysis of mutations induced by endogenous and/or exogenous genotoxic agents.

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“…Mutation spectrum analysis has shown that the rate of G to T transversions in the lung cancer of smokers (about 30%) is higher than that of non-smokers (10%–15%) [90, 91, 95]. However, experimental inhalation of environmental tobacco smoke to Big Blue mice showed that the most common mutation induced on the cII gene was G to A transition and the next was G to T transversion [96]. …”

Section: Introductionmentioning

confidence: 99%

Evaluation of in vivo mutagenesis for assessing the health risk of air pollutants

Aoki

2017

Genes and Environ

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Various kind of chemical substances, including man-made chemical products and unintended products, are emitted to ambient air. Some of these substances have been shown to be mutagenic and therefore to act as a carcinogen in humans. National pollutant inventories (e.g., Pollutant Release and Transfer Registration in Japan) have estimated release amounts of man-made chemical products, but a major concern is the release of suspended particulate matter containing potent mutagens, for example, polycyclic aromatic hydrocarbons and related compounds generated by the combustion of fossil fuel, which are not estimated by PRTR system. In situ exposure studies have revealed that DNA adducts in the lung, and possibly mutations in germline cells are induced in rodents by inhalation of ambient air, indicating that evaluating in vivo mutations is important for assessing environmental health risks. Transgenic rodent systems (Muta, Big Blue, and gpt delta) are good tools for analyzing in vivo mutations induced by a mixture of chemical substances present in the environment. Following inhalation of diesel exhaust (used as a model mixture), mutation frequency was increased in the lung of gpt delta mice and base substitutions were induced at specific guanine residues (mutation hotspots) on the target transgenes. Mutation hotspots induced by diesel exhaust were different from those induced by benzo[a]pyrene, a typical mutagen in ambient air, but nearly identical to those induced by 1,6-dinitropyrene contained in diesel exhaust. Comparison between mutation hotspots in the TP53 (p53) gene in human lung cancer (data extracted from the IARC TP53 database) and mutations we identified in gpt delta mice showed that G to A transitions centered in CGT and CGG trinucleotides were mutation hotspots on both TP53 genes in human lung cancers and gpt genes in transgenic mice that inhaled diesel exhaust. The carcinogenic potency (TD50 value) of genotoxic carcinogen was shown to be correlated with the in vivo mutagenicity (total dose per increased mutant frequency). These results suggest that the mutations identified in transgenic rodents can help identify environmental mutagens that cause cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s41021-016-0064-6) contains supplementary material, which is available to authorized users.

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New experimental data linking secondhand smoke exposure to lung cancer in nonsmokers

Cited by 19 publications

References 34 publications

Genotoxicity of tobacco smoke‐derived aromatic amines and bladder cancer: current state of knowledge and future research directions

Genotoxicity of tobacco smoke‐derived aromatic amines and bladder cancer: current state of knowledge and future research directions

A high-throughput next-generation sequencing-based method for detecting the mutational fingerprint of carcinogens

Evaluation of in vivo mutagenesis for assessing the health risk of air pollutants

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