STUDY OBJECTIVE: To review the tobacco industry's Asian environmental tobacco smoke (ETS) consultants programme, focusing on three key nations: China, Hong Kong, and Malaysia.
METHODS: Systematic keyword and opportunistic website searches of formerly private internal industry documents.
MAIN RESULTS: The release of the 1986 US Surgeon General's report on second hand smoke provoked tobacco companies to prepare for a major threat to their industry. Asian programme activities included conducting national/international symposiums, consultant "road shows" and extensive lobbying and media activities. The industry exploited confounding factors said to be unique to Asian societies such as diet, culture and urban pollution to downplay the health risks of ETS. The industry consultants were said to be "..prepared to do the kinds of things they were recruited to do".
CONCLUSIONS: The programme was successful in blurring the science on ETS and keeping the controversy alive both nationally and internationally. For the duration of the project, it also successfully dissuaded national policy makers from instituting comprehensive bans on smoking in public places.
Concentrations of 12 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were determined in 306 urine samples collected from seven Asian countries (China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam) by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The total concentrations of OH-PAHs found in the seven Asian countries were in the following increasing order: Malaysia (median: 2260 pg/mL) < Japan (4030 pg/mL) < China (5770 pg/mL) < India (6750 pg/mL) < Vietnam (8560 pg/mL) < Korea (9340 pg/mL) < Kuwait (10170 pg/mL). The measured urinary concentrations of 1-hydroxypyrene (1-PYR) in samples from Malaysia, Korea, and Japan (∼ 100 pg/mL) were similar to those reported for North America and Western Europe. The concentrations of 1-PYR in urine samples from China, India, and Vietnam were 4-10 times higher than those reported for other countries, thus far. Among the 12 OH-PAH compounds analyzed, hydroxynaphthalene (NAP: sum of 1-hydroxynaphthalene and 2-hydroxynaphthalene) was the dominant compound (accounting for 60-90% of total OH-PAHs), followed by hydroxyphenanthrene (PHEN: sum of 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, and 9-hydroxyphenanthrene [3-16%]), 2-hydroxyfluorene (3-20%), and 1-PYR (2-8%). The total daily intakes (DIs) of PAHs were estimated based on the urinary concentrations of their metabolites. The DIs of naphthalene were found to be higher for populations in Korea, Kuwait, and Vietnam (> 10 μg/day) than those of the other countries studied (∼ 5 μg/day). The DIs of phenanthrene and pyrene (> 10 μg/day) in the populations of China, India, and Vietnam were higher than those estimated for the populations in the other countries studied (∼ 5 μg/day).
Polycyclic aromatic hydrocarbons (PAHs) are primarily formed as a result of thermal treatment of food, especially barbecuing or grilling. Contamination by PAHs is due to generation by direct pyrolysis of food nutrients and deposition from smoke produced through incomplete combustion of thermal agents. PAHs are ubiquitous compounds, well-known to be carcinogenic, which can reach the food in different ways. As an important human exposure pathway of contaminants, dietary intake of PAHs is of increasing concern for assessing cancer risk in the human body. In addition, the risks associated with consumption of barbecued meat may increase if consumers use cooking practices that enhance the concentrations of contaminants and their bioaccessibility. Since total PAHs always overestimate the actual amount that is available for absorption by the body, bioaccessibility of PAHs is to be preferred. Bioaccessibility of PAHs in food is the fraction of PAHs mobilized from food matrices during gastrointestinal digestion. An in vitro human digestion model was chosen for assessing the bioaccessibility of PAHs in food as it offers a simple, rapid, low cost alternative to human and animal studies; providing insights which may not be achievable in in vivo studies. Thus, this review aimed not only to provide an overview of general aspects of PAHs such as the formation, carcinogenicity, sources, occurrence, and factors affecting PAH concentrations, but also to enhance understanding of bioaccessibility assessment using an in vitro digestion model.
Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.
Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.
One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.
Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.
As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.
The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis.
The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.
Samples of mangrove snails Nerita lineata and surface sediments were collected from nine geographical sampling sites in Peninsular Malaysia to determine the concentrations of eight metals. For the soft tissues, the ranges of metal concentrations (μg g(-1) dry weight (dw)) were 3.49-9.02 for As, 0.69-6.25 for Cd, 6.33-25.82 for Cu, 0.71-6.53 for Cr, 221-1285 for Fe, 1.03-50.47 for Pb, and 102.7-130.7 for Zn while Hg as 4.00-64.0 μg kg(-1) dw(-1). For sediments, the ranges were 21.81-59.49 for As, 1.11-2.00 for Cd, 5.59-28.71 for Cu, 18.93-62.91 for Cr, 12973-48916 for Fe, 25.36-172.57 for Pb, and 29.35-130.34 for Zn while for Hg as 2.66-312 μg kg(-1) dw(-1). To determine the ecological risks on the surface habitat sediments, sediment quality guidelines (SQGs), the geochemical indices, and potential ecological risk index (PERI) were used. Based on the SQGs, all the metals investigated were most unlikely to cause any adverse effects. Based on geoaccumulation index and enrichment factor, the sediments were also not polluted by the studied metals. The PERI values based on As, Cd, Cu, Cr, Hg, Pb and Zn in this study were found as 'low ecological risk'. In order to assess the potential health risks, the estimated daily intakes (EDI) of snails were found to be all lower than the RfD guidelines for all metals, except for Pb in some sites investigated. Furthermore, the calculated target hazard quotients (THQ) were found to be less than 1. However, the calculated total target hazard quotients (TTHQ) from all sites were found to be more than 1 for high level consumers except KPPuteh. Therefore, moderate amount of intake is advisable to avoid human health risks to the consumers.
A retrospective study was carried out to ascertain the degree of exposure to the tubercle bacillus within Ipoh Hospital. This study reveals that, over a one year period, 92 sputum positive cases were admitted to the general wards. In 11 of these cases, drug resistance was considered to be possible. The mean time from admission to the commencement of treatment was seven days for the newly diagnosed cases. This study thus documents a significant degree of in-hospital exposure to the tubercle bacillus.
Soil-transmitted helminthiasis is a common problem in communities with poor socio-environmental conditions. This study was undertaken to identify important socio-environmental predictors of soil-transmitted helminthiasis in Bachok, a rural community in Kelantan for the development and implementation of an effective prevention and control program. Of 363 children randomly sampled, 38.8% were infected with soil-transmitted helminthiasis. Risk predictors of soil-transmitted helminthiasis found to be significant after adjustment included poor household hygiene score and large household size. The probability of being infected was 0.58 amongst children with both of these risk factors.
It is important to assess indoor air quality in school classrooms where the air quality may significantly influence school children's health and performance. This study aims to determine the concentrations of PM2.5 and dust chemical compositions in indoor and outdoor school classroom located in Kuala Lumpur City Centre. The PM2.5 concentration was measured from 19th September 2017-16th February 2018 using an optical PM2.5 sensor. Indoor and outdoor dust was also collected from the school classrooms and ion and trace metal concentrations were analysed using ion chromatography (IC) and inductively couple plasma-mass spectrometry (ICP-MS) respectively. This study showed that the average indoor and outdoor 24 h PM2.5 was 11.2 ± 0.45 µg m-3 and 11.4 ± 0.44 µg m-3 respectively. The 8 h PM2.5 concentration ranged between 3.2 and 28 µg m-3 for indoor and 3.2 and 19 µg m-3 for outdoor classrooms. The highest ion concentration in indoor dust was Ca2+ with an average concentration of 38.5 ± 35.0 µg g-1 while for outdoor dust SO42- recorded the highest ion concentration with an average concentration of 30.6 ± 9.37 µg g-1. Dominant trace metals in both indoor and outdoor dust were Al, Fe and Zn. Principle component analysis-multiple linear regression (PCA-MLR) demonstrated that the major source of indoor dust was road dust (69%), while soil dominated the outdoor dust (74%). Health risk assessment showed that the hazard quotient (HQ) value for non-carcinogenic trace metals was
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
Tapioca and sweet potato are the fourth and fifth most consumed crops in Malaysia. The activity concentrations of natural radionuclides in these vegetables were assessed from two regions in Malaysia (Kedah and Penang) along with soil samples using gamma ray spectroscopy. The transfer factors of 226Ra, 232Th and 40K from soil to vegetables were calculated, and a dose assessment was performed. The activity concentrations of 226Ra, 232Th and 40K in soil samples did not show a significant variation with the regions investigated, and the average values obtained, in Bq/kg, (±SD) were as follows: 80 ± 41, 56 ± 12, 516 ± 119, respectively. The respective average activity concentrations in vegetables were as follows, in Bq/kg: (±SD) 2.0 ± 0.5, 6 ± 2, 153 ± 49. The corresponding transfer factors were calculated to be 0.03, 0.11 and 0.31 for 226Ra, 232Th and 40K, respectively. The average annual effective doses due to the exposure from soil and ingestion of vegetables were found to lie within the worldwide ranges.
The burden of colorectal cancer (CRC) is increasing worldwide especially in developing countries. This phenomenon may be attributable to lifestyle, dietary and environmental risk factors. We aimed to determine the level of 25 trace elements, their interaction with environmental risk factors, and subsequently develop a risk prediction model for CRC (RPM CRC). For the discovery phase, we used a hospital-based case-control study (CRC and non-CRC patients) and in the validation phase we analysed pre-symptomatic samples of CRC patients from The Malaysian Cohort Biobank. Information on the environmental risk factors were obtained and level of 25 trace elements measured using the ICP-MS method. CRC patients had lower Zn and Se levels but higher Li, Be, Al, Co, Cu, As, Cd, Rb, Ba, Hg, Tl, and Pb levels compared to non-CRC patients. The positive interaction between red meat intake ≥ 50 g/day and Co ≥ 4.77 µg/L (AP 0.97; 95% CI 0.91, 1.03) doubled the risk of CRC. A panel of 24 trace elements can predict simultaneously and accurate of high, moderate, and low risk of CRC (accuracy 100%, AUC 1.00). This study provides a new input on possible roles for various trace elements in CRC as well as using a panel of trace elements as a screening approach to CRC.
Air pollution is a substantial environmental threat to children and acts as acute and chronic disease risk factors alike. Several studies have previously evaluated epigenetic modifications concerning its exposure across various life stages. However, findings on epigenetic modifications as the consequences of air pollution during childhood are rather minimal. This review evaluated highly relevant studies in the field to analyze the existing literature regarding exposure to air pollution, with a focus on epigenetic alterations during childhood and their connections with respiratory health effects. The search was conducted using readily available electronic databases (PubMed and ScienceDirect) to screen for children's studies on epigenetic mechanisms following either pre- or post-natal exposure to air pollutants. Studies relevant enough and matched the predetermined criteria were chosen to be reviewed. Non-English articles and studies that did not report both air monitoring and epigenetic outcomes in the same article were excluded. The review found that epigenetic changes have been linked with exposure to air pollutants during early life with evidence and reports of how they may deregulate the epigenome balance, thus inducing disease progression in the future. Epigenetic studies evolve as a promising new approach in deciphering the underlying impacts of air pollution on deoxyribonucleic acid (DNA) due to links established between some of these epigenetic mechanisms and illnesses.
Carbon nanotubes (CNTs) are an important class of nanomaterials, which have numerous novel properties that make them useful in technology and industry. Generally, there are two types of CNTs: single-walled nanotubes (SWNTs) and multi-walled nanotubes. SWNTs, in particular, possess unique electrical, mechanical, and thermal properties, allowing for a wide range of applications in various fields, including the electronic, computer, aerospace, and biomedical industries. However, the use of SWNTs has come under scrutiny, not only due to their peculiar nanotoxicological profile, but also due to the forecasted increase in SWNT production in the near future. As such, the risk of human exposure is likely to be increased substantially. Yet, our understanding of the toxicological risk of SWNTs in human biology remains limited. This review seeks to examine representative data on the nanotoxicity of SWNTs by first considering how SWNTs are absorbed, distributed, accumulated and excreted in a biological system, and how SWNTs induce organ-specific toxicity in the body. The contradictory findings of numerous studies with regards to the potential hazards of SWNT exposure are discussed in this review. The possible mechanisms and molecular pathways associated with SWNT nanotoxicity in target organs and specific cell types are presented. We hope that this review will stimulate further research into the fundamental aspects of CNTs, especially the biological interactions which arise due to the unique intrinsic characteristics of CNTs.
IntroductionMany epidemiological studies have demonstrated associations between air pollution levels and human health in terms of hospital admissions. The aim of this paper is to gather evidence concerning air pollution effects on the risk of hospital admission. We hypothesised that increase in: particulate matter (PM), ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), and sulphur dioxide (SO2) levels would be associated with the increasing trend of hospital admission.MethodsA systematic review of literature was carried out. Literature search was done in Sage, Ovid Medline, Science Direct, Wiley and ProQuest from 2010 to 2016 using keywords "hospital admission and air pollution". Studies of any relevant design were included if they presented original data, included at least one analysis where hospital admission was the specific outcome, and one or more of the following exposures were investigated: PM, O3, CO, NO2 and SO2.ResultsA total of 175 potential studies were identified by the search. Twenty two studies qualified for the review. Air pollution was noted to have an excessive risk of 3.46 (95%CI, 1.67, 5.27) of total hospital admissions. Cardiovascular admission was noted to have an increased risk of hospitalization for PM2.5 of 1.5 to 2.0; PM10 (1.007 to 2.7); NO2 (1.04 to 1.17) and SO2 (1.007). For respiratory admission, PM2.5 can caused an increased risk of hospitalization by 1.1 to 1.8; PM10 (1.007 to 1.13); NO2 (1.08 to 1.94) and SO2 (1.02). While O3 have minimal effect on COPD and stroke, CO does not influence in the effect of these hospitalization.ConclusionThe exposure to air pollutants confers an increased risk of admission of several disease. Our findings call for greater awareness of environmental protection and the implementation of effective measures to improve the quality of air, which may reduce the risks of adverse effects on the population's health.