Recently, Ng et al. reported that the A:T > T:A substitutions, proposed to be a signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients' exposure history is the key to determine the "culprit" of the A:T > T:A mutations. Apparently, without estimation of the patients' exposure history, the conclusion of Ng et al. is unpersuasive and misleading.
Aristolochic Acids ; toxicity ; Carcinogens ; toxicity ; Carcinoma, Hepatocellular ; chemically induced ; genetics ; China ; Environment ; Humans ; Liver Neoplasms ; chemically induced ; genetics ; Mutation ; Taiwan ; Tobacco ; toxicity ; Vinyl Chloride ; toxicity

The present review summarizes the results of several follow-up studies assessing an asbestos product manufacturing plant in Chongqing, China, and discusses three controversial issues related to the carcinogenicity of asbestos. The first issue is the amphibole hypothesis, which asserts that the carcinogenicity of asbestos is limited to amphiboles, such as crocidolite, but not serpentines, such as chrysotile. However, considering the possible multiple component of asbestos carcinogenicity in the presence of tobacco smoke or other carcinogens, chrysotile cannot be regarded as non-carcinogenic. Additionally, in a practical sense, it is not possible to assume "pure" chrysotile due to its ubiquitous contamination with tremolite, which is a type of amphibole. Thus, as the International Agency for Research on Cancer (IARC) assessed, all forms of asbestos including chrysotile should be regarded carcinogenic to humans (Group 1). The second issue is the chrysotile/tremolite paradox, which is a phenomenon involving predominant levels of tremolite in the lung tissues of individuals who worked in locations with negligible levels of tremolite due to the exclusive use of chrysotile. Four possible mechanisms to explain this paradox have been proposed but this phenomenon does not support the claim that amphibole is inert. The final issue discussed is the textile mystery, i.e., the higher incidence of cancer in asbestos textile plants compared to asbestos mines where the same asbestos was produced and the exposure levels were comparable. This phenomenon was first reported in North America followed by UK and then in the present observations from China. Previously, levels of fiber exposure were calculated using a universal converting coefficient to estimate the mass concentration versus fiber concentration. However, parallel measurements of fiber and mass concentrations in the workplace and exposed air indicated that there are wide variations in the fiber/mass ratio, which unjustifies the universal conversion. It is possible that contamination by airborne non-fibrous particles in mines with mass fiber conversion led to the overestimation of fiber concentrations and resulted in the textile mystery. Although the use and manufacturing of asbestos has been banned in Japan, more than 10 million tons of asbestos had been imported and the majority remains in existing buildings. Thus, efforts to control asbestos exposure should be continued.
Asbestos ; classification ; toxicity ; Asbestos, Amphibole ; toxicity ; Asbestos, Serpentine ; toxicity ; Carcinogens ; China ; Follow-Up Studies ; Humans ; Lung Neoplasms ; chemically induced ; epidemiology ; Manufacturing and Industrial Facilities ; statistics & numerical data ; Mining ; statistics & numerical data ; Occupational Diseases ; epidemiology ; Occupational Exposure ; adverse effects ; Textiles ; Tobacco Smoking ; epidemiology

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin (Prx) expression induced by NNK during carcinogenesis. Characterization of Prx genes from hamster was performed using bioinformatics. V79 cells were induced with different concentrations of NNK (0.1-0.4 mg/mL), and the expression levels of six Prx genes (Prx1-Prx6) were measured by qRT-PCR 24 h following NNK treatment. Prx gene expression was induced by NNK stress, and the highest transcription levels were induced by over 20.42-fold relative to that of the control. NNK induced alterations in Prx expression over the course of lung cancer, which means Prxs may play important roles in ROS detoxification under NNK stress and their functions are complementary.
Animals ; Carcinogens ; administration & dosage ; toxicity ; Cell Line ; Cell Survival ; Cricetinae ; Cricetulus ; Dose-Response Relationship, Drug ; Gene Expression Regulation ; drug effects ; Nitrosamines ; administration & dosage ; toxicity ; Peroxiredoxins ; genetics ; metabolism

No abstract available.
Adult ; Carcinogens/toxicity ; Environmental Exposure ; Genome, Human/radiation effects ; Humans ; Neoplasms, Radiation-Induced/epidemiology/etiology/*genetics ; *Nuclear Power Plants ; Republic of Korea/epidemiology ; Thyroid Neoplasms/epidemiology/etiology/*genetics

Benzene is classified as Group 1 carcinogen by IARC. It has been found that benzene induces hematotoxicity even in low dose exposure. The identification of key events during benzene induced hematotoxicty leads to adjustment of occupational exposure limits of benzene. In this review, we focus on the exposure, metabolism, target organs, key epigenetic changes, toxicty effects and end points of low-dose chronic benzene exposure induced hematotoxicity and finally discuss the perspectives on the future study of this area.
Benzene ; toxicity ; Carcinogens ; toxicity ; Epigenesis, Genetic ; Humans ; Occupational Exposure

OBJECTIVETo investigate the changes of miR-155 and its target genes in colitis-associated carcinogenesis.

METHODSColitis-associated colon cancer was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice of three different stages during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment and a DSS only group representing chronic inflammation without cancer were set up as well. Colon tissue was collected and expression of miR-155 in the colon tissues was measured by real-time fluorescent quantitative PCR. TargetScan and PicTar were used to predict potential target genes of miR-155, which were then preliminarily screened with our gene expression microarray database of AOM-DSS mouse model. Regular PCR was used to confirm the changes of the expression of these potential target genes in AOM-DSS mouse model.

RESULTSColitis-associated colon cancer was effectively induced by azoxymethane and dextran sulfate sodium in C57BL/6 mice. Histological examination revealed that the evolution process was sequentially from normal, mild dysplasia, moderate dysplasia, and severe dysplasia to adenocarcinoma in the AOM-DSS mouse model. The level of miR-155 was gradually elevated with the formation of colitis-associated colon cancer. There was no significant difference between the levels of miR-155 expression in the DSS group (0.005 6 ± 0.003 7) and control group (0.012 0 ± 0.005 1) (P > 0.05), but the level of miR-155 in the AD3 group (0.054 4 ± 0.027 0) was significantly higher than that of the DSS group (0.005 6 ± 0.003 7)(P < 0.01). No significant change of miR-155 expression was found in the DSS only group. The relative expression levels of miR-155 in the control group, DSS only group and AD3 group were 0.012 0 ± 0.005 1, 0.005 6 ± 0.003 7, 0.054 4 ± 0.027 0, respectively. Data analysis with the gene expression microarray showed that Tle4, Kcna1, Itk, Bcorl1, Cacna1c, Rspo2 and Foxo3 were potential target genes of miR-155 in the AOM-DSS mouse model. Changes of Kcna1 and Cacna1c in the AOM-DSS mouse model were validated to be consistent with the changes obtained with the gene expression microarray.

CONCLUSIONThe up-regulation of miR-155 is related to colitis-associated carcinogenesis, but is irrelevant to chronic inflammation in the mouse model.

Adenocarcinoma ; chemically induced ; genetics ; metabolism ; Animals ; Azoxymethane ; toxicity ; Carcinogens ; toxicity ; Cocarcinogenesis ; Colitis ; chemically induced ; genetics ; metabolism ; Colon ; metabolism ; Colonic Neoplasms ; chemically induced ; genetics ; metabolism ; Dextran Sulfate ; toxicity ; Gene Expression Profiling ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; metabolism ; Precancerous Conditions ; chemically induced ; genetics ; metabolism ; Up-Regulation

The legal scope and criteria for occupational cancer in Korea was out of date. The aim of this study was to review the current criteria for occupational cancer and amend the existent criteria on the basis of recent scientific evidence. The scientific evidence and the legal list of occupational cancer were analyzed to identify the causes of occupational cancer on a global scale. The relationship between compensated occupational cancer cases and carcinogen exposure in Korea was examined. The factors associated with specific causes and target cancers were determined to produce additional criteria. Five-hundred and nineteen cases of 2,468 were awarded compensation for occupational cancer including lung, malignant mesothelioma, lymphohematopoietic, and liver cancers from January 2000 to October 2012. Between 1996 and 2005, benzene accounted for 84.4% of cases, and between 1999 and 2005, asbestos was associated with 62.3% of cases. Fourteen novel causative agents and 12 additional target cancers were identified and the final guidelines were amended to include 23 causative agents and 21 target cancers. This amendment of the criteria for occupational cancer represents the widest change in Korean history and is expected to improve the understanding of occupational cancer by providing an up-to-date and accurate reference guide.
Asbestos/toxicity ; Benzene/toxicity ; Carcinogens/toxicity ; Female ; Humans ; Insurance, Health/*economics ; Middle Aged ; Neoplasms/chemically induced/*economics ; Occupational Diseases/*economics/mortality ; Occupational Exposure/*adverse effects ; Republic of Korea ; Workers' Compensation/*economics/legislation & jurisprudence/standards

The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population.
Air Pollutants ; toxicity ; Air Pollution ; adverse effects ; Animals ; Asia ; Carcinogens, Environmental ; toxicity ; China ; Environmental Exposure ; Humans ; International Agencies ; Lung Neoplasms ; etiology ; Neoplasms ; etiology ; Particulate Matter ; toxicity ; Risk Factors

Once considered a taboo topic or stigma, cancer is the number one public health enemy in the world. Once a product of an almost untouchable industry, tobacco is indisputably recognized as a major cause of cancer and a target for anticancer efforts. With the emergence of new economic powers in the world, especially in highly populated countries such as China, air pollution has rapidly emerged as a smoking gun for cancer and has become a hot topic for public health debate because of the complex political, economic, scientific, and technologic issues surrounding the air pollution problem. This editorial and the referred articles published in this special issue of the Chinese Journal of Cancer discuss these fundamental questions. Does air pollution cause a wide spectrum of cancers? Should air pollution be considered a necessary evil accompanying economic transformation in developing countries? Is an explosion of cancer incidence coming to China and how soon will it arrive? What must be done to prevent this possible human catastrophe? Finally, the approaches for air pollution control are also discussed.
Air Pollution ; adverse effects ; Carcinogens, Environmental ; toxicity ; China ; Humans ; Neoplasms ; etiology ; Risk Factors ; Smoking ; adverse effects

Air pollution in China comes from multiple sources, including coal consumption, construction and industrial dust, and vehicle exhaust. Coal consumption in particular directly determines the emissions of three major air pollutants: dust, sulfur dioxide (SO(2)), and nitrogen oxide (NOx). The rapidly increasing number of civilian vehicles is expected to bring NOx emission to a very high level. Contrary to expectations, however, existing data show that the concentrations of major pollutants [particulate matter-10 (PM10), SO(2), and nitrogen dioxide (NO(2))] in several large Chinese cities have declined during the past decades, though they still exceed the national standards of ambient air quality. Archived data from China does not fully support that the concentrations of pollutants directly depend on local emissions, but this is likely due to inaccurate measurement of pollutants. Analyses on the cancer registry data show that cancer burden related to air pollution is on the rise in China and will likely increase further, but there is a lack of data to accurately predict the cancer burden. Past experience from other countries has sounded alarm of the link between air pollution and cancer. The quantitative association requires dedicated research as well as establishment of needed monitoring infrastructures and cancer registries. The air pollution-cancer link is a serious public health issue that needs urgent investigation.
Air Pollutants ; toxicity ; Air Pollution ; adverse effects ; Carcinogens, Environmental ; toxicity ; China ; Coal ; Humans ; Neoplasms ; etiology ; Nitrogen Dioxide ; toxicity ; Particulate Matter ; toxicity ; Sulfur Dioxide ; toxicity ; Vehicle Emissions ; toxicity