Structural and mechanistic insights into the transport of aristolochic acids and their active metabolites by human serum albumin.

Aristolochic acids I and II (AA-I/II) are carcinogenic principles of Aristolochia plants, which have been employed in traditional medicinal practices and discovered as food contaminants. While the deleterious effects of AAs are broadly acknowledged, there is a dearth of information to define the mechanisms underlying their carcinogenicity. Following bioactivation in the liver, N-hydroxyaristolactam and N-sulfonyloxyaristolactam metabolites are transported via circulation and elicit carcinogenic effects by reacting with cellular DNA. In this study, we apply DNA adduct analysis, X-ray crystallography, isothermal titration calorimetry, and fluorescence quenching to investigate the role of human serum albumin (HSA) in modulating AA carcinogenicity. We find that HSA extends the half-life and reactivity of N-sulfonyloxyaristolactam-I with DNA, thereby protecting activated AAs from heterolysis. Applying novel pooled plasma HSA crystallization methods, we report high-resolution structures of myristic acid-enriched HSA (HSAMYR) and its AA complexes (HSAMYR/AA-I and HSAMYR/AA-II) at 1.9 Å resolution. While AA-I is located within HSA subdomain IB, AA-II occupies subdomains IIA and IB. ITC binding profiles reveal two distinct AA sites in both complexes with association constants of 1.5 and 0.5 · 106 M-1 for HSA/AA-I versus 8.4 and 9.0 · 105 M-1 for HSA/AA-II. Fluorescence quenching of the HSA Trp214 suggests variable impacts of fatty acids on ligand binding affinities. Collectively, our structural and thermodynamic characterizations yield significant insights into AA binding, transport, toxicity, and potential allostery, critical determinants for elucidating the mechanistic roles of HSA in modulating AA carcinogenicity.

"Characterization of residential proximity to sources of environmental carcinogens in clusters of Acute Lymphoblastic Leukemia in San Luis Potosi, Mexico".

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is the most prevalent neoplasia in children and teenagers in Mexico. Although epidemiological data supports that children's residence close to emissions from vehicular traffic or industrial processes increases the risk of ALL; and the IARC states that benzene, PAHs, and PM 2.5 are well-known environmental carcinogens, there is a gap in linking these carcinogenic hazards with the sources and their distribution from scenario perspective. AIM: To identify ALL clusters in the population under 19 years of age and characterize the environment at the neighborhood level by integrating information on sources of carcinogenic exposure using spatial analysis techniques in the Metropolitan Area of San Luis Potosi, Mexico. METHODS: Using the Kernel Density test, we designed an ecological study to identify ALL clusters from incident cases in the population under 19 years of age. A multicriteria analysis was conducted to characterize the risk at the community level from carcinogenic sources. A hierarchical cluster analysis was performed to characterize risk at the individual level based on carcinogenic source count within 1 km for each ALL case. RESULTS: Eight clusters of carcinogenic sources were located within the five identified ALL clusters. The multicriteria analysis showed high-risk areas (by density of carcinogenic source) within ALL clusters. CONCLUSIONS: This study has a limited source and amount of available data on ALL cases, so selection bias is present as well as the inability to rule out residual confounding factors, since covariates were not included. However, in this study, children living in environments with high vehicular density, gas stations, brick kilns, incinerators, commercial establishments burning biomass, or near industrial zones may be at higher risk for ALL.

Modifiable risk factors for cancer in the middle East and North Africa: a scoping review.

PURPOSE: This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region's adult population, highlighting opportunities to enhance cancer prevention programs. DESIGN: We systematically searched the PubMed, Science Direct, and CINAHL, EMBASE, and Cochrane Library databases from 1997 to 2022 for articles reporting on the impact of modifiable risk factors on adult patients with cancer in the MENA region. RESULTS: The review identified 42 relevant articles, revealing that tobacco consumption, obesity, physical inactivity, and diet are significant modifiable risk factors for cancer in the region. Tobacco smoking is a leading cause of lung, bladder, squamous cell carcinoma, and colorectal cancer. A shift towards a westernized, calorie-dense diet has been observed, with some evidence suggesting that a Mediterranean diet may be protective against cancer. Obesity is a known risk factor for cancer, particularly breast malignancy, but further research is needed to determine its impact in the MENA region. Physical inactivity has been linked to colorectal cancer, but more studies are required to establish this relationship conclusively. Alcohol consumption, infections, and exposure to environmental carcinogens are additional risk factors, although the literature on these topics is limited. CONCLUSION: The review emphasizes the need for further research and the development of targeted cancer prevention strategies in the MENA region.

Unraveling Therapeutic Opportunities and the Diagnostic Potential of microRNAs for Human Lung Cancer.

Lung cancer is a major public health problem and a leading cause of cancer-related deaths worldwide. Despite advances in treatment options, the five-year survival rate for lung cancer patients remains low, emphasizing the urgent need for innovative diagnostic and therapeutic strategies. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets for lung cancer due to their crucial roles in regulating cell proliferation, differentiation, and apoptosis. For example, miR-34a and miR-150, once delivered to lung cancer via liposomes or nanoparticles, can inhibit tumor growth by downregulating critical cancer promoting genes. Conversely, miR-21 and miR-155, frequently overexpressed in lung cancer, are associated with increased cell proliferation, invasion, and chemotherapy resistance. In this review, we summarize the current knowledge of the roles of miRNAs in lung carcinogenesis, especially those induced by exposure to environmental pollutants, namely, arsenic and benzopyrene, which account for up to 1/10 of lung cancer cases. We then discuss the recent advances in miRNA-based cancer therapeutics and diagnostics. Such information will provide new insights into lung cancer pathogenesis and innovative diagnostic and therapeutic modalities based on miRNAs.

Histone methylation in pre-cancerous liver diseases and hepatocellular carcinoma: recent overview

Hepatocellular carcinoma (HCC) is the prevalent form of liver cancer in adults and the fourth most common cause of cancer-related death worldwide. HCC predominantly arises in the context of cirrhosis as a result of chronic liver disease, injury and inflammation. Full-blown HCC has poor prognosis because it is highly aggressive and resistant to therapy. Consequently, interventions that can prevent or restrain HCC emergence from pre-cancerous diseased liver are a desirable strategy. Histone methylation is a dynamic, reversible epigenetic modification involving the addition or removal of methyl groups from lysine, arginine or glutamine residues. Aberrant activity of histone methylation writers, erases and readers has been implicated in several cancer types, including HCC. In this review, we provide an overview of research on the role of histone methylation in pre-cancerous and cancerous HCC published over the last 5 years. In particular, we present the evidence linking environmental factors such as diet, viral infections and carcinogenic agents with dysregulation of histone methylation during liver cancer progression with the aim to highlight future therapeutic possibilities (AU)

Helicobacter pylori plus N-Methyl-N'-nitro-N-nitrosoguanidine: DNA damage and repair: Malignant transformation of human esophageal epithelial cells.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG), found in pickled foods and in chlorinated water, has been used to induce malignant transformation and gastrointestinal cancer in rats. Helicobacter pylori (HP) is implicated in human gastric cancer and possibly also in esophageal cancer. These two agents - one chemical and the other biological - might act together to induce esophageal cancer. In this study, human esophageal epithelial cells (HEECs) were divided into four groups: HP, MNNG, HP + MNNG, and control. The HP-to-HEEC ratio was 100:1. Cells were exposed for 6 h and then passaged until malignant transformation. HEEC at early, intermediate, and late stages of malignant transformation were used for proliferation, cell-cycle, and invasion assays. The alkaline comet assay was performed and expression of proteins, including γ-H2AX and PAXX, was studied by western blotting, to explore DNA damage and repair processes. Measurements of cell morphology, soft-agar clone formation, and invasiveness, and a nude mouse xenograft model, were used to examine malignancy. The effect of HP was stronger than that of MNNG. The combination HP + MNNG exerted a stronger malignant transformation effect than either HP or MNNG alone. Mechanisms of this combined carcinogenesis may include promotion of cell proliferation, perturbation of the cell cycle, promotion of invasiveness, DNA double-strand break induction, or PAXX inhibition.

Histone methylation in pre-cancerous liver diseases and hepatocellular carcinoma: recent overview.

Hepatocellular carcinoma (HCC) is the prevalent form of liver cancer in adults and the fourth most common cause of cancer-related death worldwide. HCC predominantly arises in the context of cirrhosis as a result of chronic liver disease, injury and inflammation. Full-blown HCC has poor prognosis because it is highly aggressive and resistant to therapy. Consequently, interventions that can prevent or restrain HCC emergence from pre-cancerous diseased liver are a desirable strategy. Histone methylation is a dynamic, reversible epigenetic modification involving the addition or removal of methyl groups from lysine, arginine or glutamine residues. Aberrant activity of histone methylation writers, erases and readers has been implicated in several cancer types, including HCC. In this review, we provide an overview of research on the role of histone methylation in pre-cancerous and cancerous HCC published over the last 5 years. In particular, we present the evidence linking environmental factors such as diet, viral infections and carcinogenic agents with dysregulation of histone methylation during liver cancer progression with the aim to highlight future therapeutic possibilities.

Role of RNA modifications in carcinogenesis and carcinogen damage response.

The field of epitranscriptomics encompasses the study of post-transcriptional RNA modifications and their regulatory enzymes. Among the numerous RNA modifications, N6 -methyladenosine (m6 A) has been identified as the most common internal modification of messenger RNA (mRNA). Although m6 A modifications were first discovered in the 1970s, advances in technology have revived interest in this field, driving an abundance of research into the role of RNA modifications in various biological processes, including cancer. As analogs to epigenetic modifications, RNA modifications also play an important role in carcinogenesis by regulating gene expression post-transcriptionally. A growing body of evidence suggests that carcinogens can modulate RNA modifications to alter the expression of oncogenes or tumor suppressors during cellular transformation. Additionally, the expression and activity of the enzymes that regulate RNA modifications can be dysregulated and contribute to carcinogenesis, making these enzymes promising targets of drug discovery. Here we summarize the roles of RNA modifications during carcinogenesis induced by exposure to various environmental carcinogens, with a main focus on the roles of the most widely studied m6 A mRNA methylation.

Reprogramming of glycolysis by chemical carcinogens during tumor development.

Indiscriminate usage and mismanagement of chemicals in the agricultural and industrial sectors have contaminated different environmental compartments. Exposure to these persistent and hazardous pollutants like heavy metals, endocrine disruptors, aromatic hydrocarbons, and pesticides can result in various health adversities, including cancer. Chemical carcinogens follow a similar pattern of carcinogenesis, like oxidative stress, chromosomal aberration, DNA double-strand break, mismatch repair, and misregulation of oncogenic and/or tumor suppressors. Out of several cancer-associated endpoints, cellular metabolic homeostasis is the commonest to be deregulated upon chemical exposure. Chemical carcinogens hamper glycolytic reprogramming to fuel the malignant transformation of the cells and/or promote cancer progression. Several regulators like Akt, ERK, Ras, c-Myc, HIF-1α, and p53 regulate glycolysis in chemical-induced carcinogenesis. However, the deregulation of the anabolic biochemistry of glucose during chemical-induced carcinogenesis remains to be uncovered. This review comprehensively covers the environmental chemical-induced glycolytic shift during carcinogenesis and its mechanism. The focus is also to fill the major gaps associated with understanding the fairy tale between environmental carcinogens and metabolic reprogramming. Although evidence from studies regarding glycolytic reprogramming in chemical carcinogenesis provides valuable insights into cancer therapy, exposure to a mixture of toxicants and their mechanism of inducing carcinogenesis still needs to be studied.

The Mutagenic Impact of Environmental Exposures in Human Cells and Cancer: Imprints Through Time.

During life, the DNA of our cells is continuously exposed to external damaging processes. Despite the activity of various repair mechanisms, DNA damage eventually results in the accumulation of mutations in the genomes of our cells. Oncogenic mutations are at the root of carcinogenesis, and carcinogenic agents are often highly mutagenic. Over the past decade, whole genome sequencing data of healthy and tumor tissues have revealed how cells in our body gradually accumulate mutations because of exposure to various mutagenic processes. Dissection of mutation profiles based on the type and context specificities of the altered bases has revealed a variety of signatures that reflect past exposure to environmental mutagens, ranging from chemotherapeutic drugs to genotoxic gut bacteria. In this review, we discuss the latest knowledge on somatic mutation accumulation in human cells, and how environmental mutagenic factors further shape the mutation landscapes of tissues. In addition, not all carcinogenic agents induce mutations, which may point to alternative tumor-promoting mechanisms, such as altered clonal selection dynamics. In short, we provide an overview of how environmental factors induce mutations in the DNA of our healthy cells and how this contributes to carcinogenesis. A better understanding of how environmental mutagens shape the genomes of our cells can help to identify potential preventable causes of cancer.

Dysregulations of long non-coding RNAs - The emerging "lnc" in environmental carcinogenesis.

Long non-coding RNAs (lncRNAs) refer to a class of RNA molecules that are more than 200 nucleotides in length and usually lack protein-coding capacity. LncRNAs play important roles in regulating gene expression as well as many aspects of normal physiological processes. Dysregulations of lncRNA expressions and functions are considered to be critically involved in the development and progression of many diseases especially cancer. The lncRNA research in the field of cancer biology over the past decade reveals that a large number of lncRNAs are dysregulated in various types of cancer and that dysregulated lncRNAs may play important roles in cancer initiation, metastasis and therapeutic responses. Metal carcinogens and other common environmental carcinogens such as polycyclic aromatic hydrocarbons, fine particular matters, cigarette smoke, ultraviolet and ionizing radiation are important cancer etiology factors. However, the mechanisms of how metal carcinogens and other common environmental carcinogen exposures initiate cancer and promote cancer progression remain largely unknown. Accumulating evidence show that exposure to metal carcinogens and other common environmental carcinogens dysregulate lncRNA expression in various model systems, which may offer novel mechanistic insights for environmental carcinogenesis. This review will first provide a brief introduction about lncRNA biology and the mechanisms of lncRNA functions, followed by summarizing and discussing recent studies about lncRNA dysregulation by metal carcinogen and other common environment carcinogen exposures and the potential roles of dysregulated lncRNAs in environmental carcinogenesis. A perspective for future studies in this emerging and important field is also presented.

Factores etiológicos y caracterización de pacientes con cáncer de pulmón en el Instituto Nacional del Cáncer, Paraguay

RESUMEN Introducción: el cáncer de pulmón es un problema de Salud Pública en el mundo y en nuestro país por su alta mortalidad e incidencia. Los carcinógenos medioambientales y el tabaquismo están directamente relacionados como factores de riesgo. Objetivo: Caracterizar los factores etiológicos de fumador activo y carcinógenos medioambientales de los pacientes con cáncer de pulmón detectados durante 9 años en el Instituto Nacional del Cáncer, Paraguay. Metodología: estudio observacional retrospectivo descriptivo analítico de una base de datos del período 2004-2013. Las variables medidas fueron datos demográficos, carga tabáquica, tabaquismo, la exposición a carcinógenos medioambientales categoría I. Resultados: se incluyeron 478 pacientes con cáncer pulmonar, 88,1% de sexo masculino y 11,9% femenino. La edad promedio del sexo masculino fue 60±10 años y del sexo femenino 58±12 años. La prevalencia de exposición carcinógenos medioambientales categoría I fue 36,90%. La media del índice tabáquico fue 4,48±20. El modelo de regresión lineal múltiple entre exposición ambiental, tabaquismo y tipo histológico para predecir la severidad clínica fue 3,6%. En el análisis de regresión logística de la relación de tipos histológicos con tabaquismo, género y exposición ambiental no mejoran el modelo de predicción. Conclusiones: Los factores etiológicos relacionados con carcinógenos medioambientales estuvieron presentes en más de un tercio de la población, el hábito tabáquico es mayor en hombres que en mujeres. El tipo histológico más frecuente para ambos sexos, con y sin el hábito tabáquico, es el carcinoma de células no pequeñas.

ABSTRACT Introduction: Lung cancer is a public health problem in the world and in our country due to its high mortality and incidence. Environmental carcinogens and smoking are directly related as risk factors. Objective: To characterize the etiological factors of active smokers and environmental carcinogens of patients with lung cancer detected during 9 years at the National Cancer Institute, Paraguay. Methodology: Retrospective observational descriptive analytical study of a database for the period 2004-2013. The variables measured were demographic data, smoking load, smoking, exposure to category I environmental carcinogens. Results: Four hundred seventy-eight patients with lung cancer, 88.1% male and 11.9% female were included. The mean age of the male sex was 60±10 years and 58±12 years of the female age. The prevalence of exposure to category I environmental carcinogens was 36.90%. The mean smoking index was 4.48±20. The multiple linear regression model between environmental exposure, smoking and histological type to predict clinical severity was 3.6%. In the logistic regression analysis of the relationship of histological types with smoking, gender and environmental exposure, the prediction model was not improved. Conclusions: The etiological factors related to environmental carcinogens were present in more than one third of the population, and smoking was greater in men than in women. The most frequent histological type for both sexes, with and without the smoking habit, was non-small cell carcinoma.

32P-Postlabeling Analysis of DNA Adducts.

32P-Postlabeling analysis is an ultra-sensitive method for the detection of DNA adducts, such as those formed directly by the covalent binding of carcinogens and mutagens to bases in DNA, and other DNA lesions resulting from modification of bases by endogenous or exogenous agents (e.g., oxidative damage). The procedure involves four main steps: enzymatic digestion of DNA sample; enrichment of the adducts; radiolabeling of the adducts by T4 kinase-catalyzed transference of 32P-orthophosphate from [γ-32P]ATP; chromatographic separation of labeled adducts, and detection and quantification by means of their radioactive decay. Using 10 µg of DNA or less, it is capable of detecting adduct levels as low as 1 adduct in 109-1010 normal nucleotides. It is applicable to a wide range of investigations, including monitoring human exposure to environmental or occupational carcinogens, determining whether a chemical has genotoxic properties, analysis of the genotoxicity of complex mixtures, elucidation of the pathways of activation of carcinogens, and monitoring DNA repair.

Transplacental exposure to carcinogens and risks to children: evidence from biomarker studies and the utility of omic profiling.

The factors underlying the increasing rates and the geographic variation of childhood cancers are largely unknown. Epidemiological studies provide limited evidence for a possible role in the etiology of certain types of childhood cancer of the exposure of pregnant women to environmental carcinogens (e.g., tobacco smoke and pesticides); however, such evidence is inadequate to allow definitive conclusions. Complementary evidence can be obtained from biomarker-based population studies. Such studies have demonstrated that, following exposure of pregnant mothers, most environmental carcinogens reach the fetus and, in many cases, induce therein genotoxic damage which in adults is known to be associated with increased cancer risk, implying that environmental carcinogens may contribute to the etiology of childhood cancer. During recent years, intermediate disease biomarkers, obtained via omic profiling, have provided additional insights into the impact of transplacental exposures on fetal tissues which, in some cases, are also compatible with a precarcinogenic role of certain in utero exposures. Here we review the epidemiological and biomarker evidence and discuss how further research, especially utilizing high-density profiling, may allow a better evaluation of the links between in utero environmental exposures and cancer in children.

The evidence of human exposure to glyphosate: a review.

BACKGROUND: Despite the growing and widespread use of glyphosate, a broad-spectrum herbicide and desiccant, very few studies have evaluated the extent and amount of human exposure. OBJECTIVE: We review documented levels of human exposure among workers in occupational settings and the general population. METHODS: We conducted a review of scientific publications on glyphosate levels in humans; 19 studies were identified, of which five investigated occupational exposure to glyphosate, 11 documented the exposure in general populations, and three reported on both. RESULTS: Eight studies reported urinary levels in 423 occupationally and para-occupationally exposed subjects; 14 studies reported glyphosate levels in various biofluids on 3298 subjects from the general population. Average urinary levels in occupationally exposed subjects varied from 0.26 to 73.5 µg/L; environmental exposure urinary levels ranged from 0.16 to 7.6 µg/L. Only two studies measured temporal trends in exposure, both of which show increasing proportions of individuals with detectable levels of glyphosate in their urine over time. CONCLUSIONS: The current review highlights the paucity of data on glyphosate levels among individuals exposed occupationally, para-occupationally, or environmentally to the herbicide. As such, it is challenging to fully understand the extent of exposure overall and in vulnerable populations such as children. We recommend further work to evaluate exposure across populations and geographic regions, apportion the exposure sources (e.g., occupational, household use, food residues), and understand temporal trends.

Environmental Carcinogenesis and Transgenerational Transmission of Carcinogenic Risk: From Genetics to Epigenetics.

The dominant pathogenic model, somatic mutation theory (SMT), considers carcinogenesis as a 'genetic accident' due to the accumulation of 'stochastic' DNA mutations. This model was proposed and accepted by the scientific community when cancer mainly affected the elderly, but it does not explain the epidemiological observation of the continuous increase in cancer incidence among children and young adults. Somatic mutation theory has been proposed for a revision based on the emerging experimental evidence, as it does not fully address some issues that have proven to be crucial for carcinogenesis, namely: the inflammatory context of cancer; the key role played by the stroma, microenvironment, endothelial cells, activated macrophages, and surrounding tissues; and the distorted developmental course followed by the neoplastic tissue. Furthermore, SMT is often not able to consider either the existence of specific mutations resulting in a well-defined cancer type, or a clear relationship between mutations and tumor progression. Moreover, it does not explain the mechanism of action of the non-mutagenic and environmental carcinogens. In the last decade, cancer research has highlighted the prominent role of an altered regulation of gene expression, suggesting that cancer should be considered as a result of a polyclonal epigenetic disruption of stem/progenitor cells, mediated by tumour-inducing genes. The maternal and fetal exposure to a wide range of chemicals and environmental contaminants is raising the attention of the scientific community. Indeed, the most powerful procarcinogenic mechanisms of endocrine disruptors and other pollutants is linked to their potential to interfere epigenetically with the embryo-fetal programming of tissues and organs, altering the regulation of the genes involved in the cell cycle, cell proliferation, apoptosis, and other key signaling pathways. The embryo-fetal exposure to environmental, stressful, and proinflammatory triggers (first hit), seems to act as a 'disease primer', making fetal cells and tissues more susceptible to the subsequent environmental exposures (second hit), triggering the carcinogenic pathways. Furthermore, even at the molecular level, in carcinogenesis, 'epigenetics precedes genetics' as global DNA hypomethylation, and the hypermethylation of tumor suppressor genes are common both in cancerous and in precancerous cells, and generally precede mutations. These epigenetic models may better explain the increase of cancer and chronic/degenerative diseases in the last decades and could be useful to adopt appropriate primary prevention measures, essentially based on the reduction of maternal-fetal and child exposure to several procarcinogenic agents and factors dispersed in the environment and in the food-chains, as recently suggested by the World Health Organization.

Industry and geographic patterns of use and emission of carcinogens in Ontario, Canada, 2011-2015.

OBJECTIVES: The goal of this study was to leverage data from two environmental regulatory initiatives, Ontario's Toxics Reduction Act (TRA) and Canada's National Pollutant Release Inventory (NPRI), to assess their ability to monitor trends in the use and emission of carcinogens by industry sector in Ontario. METHODS: Data reported to the TRA and NPRI by industrial facilities in Ontario were retrieved from 2011 to 2015. Twenty-six known and suspected carcinogens were identified (IARC) and the trends in the use and emission were evaluated by industry sector. The locations of industrial facilities that used and released carcinogens were mapped by Public Health Unit (PHU). RESULTS: Chemical manufacturing and primary metal manufacturing sectors accounted for 84% of all reported industrial use of carcinogens during the period 2011-2015. The largest source of carcinogen emissions came from facilities in the primary metal manufacturing and paper manufacturing sectors. The largest number of industrial facilities that reported the use and release of carcinogens were located in the City of Toronto and Peel Region PHUs. Overall, the use of carcinogens across all sectors appeared to decrease by 8%, while emissions increased by about 2%. CONCLUSION: The results of this study show the need to reduce the use and emission of select carcinogens in priority industry sectors. Environmental reporting programs, such as the TRA and NPRI, can serve as important tools in cancer prevention by tracking potential carcinogen exposures in the environment and in the workplace.

Measuring public knowledge, attitudes, and behaviors related to radon to inform cancer control activities and practices.

Radon exposure is the second leading risk factor for lung cancer among smokers and the leading risk factor among non-smokers. Radon concentrated in lower levels of homes/buildings can be reduced if found, thus lowering lung cancer risk. The objective of this study was to measure radon knowledge in diverse populations, with varying radon-related laws, to inform radon-related cancer control practices and activities. A survey was mailed to 3000 homebuyers who purchased single-family homes; 995 responses (33%) were received. Overall, 86% of respondents heard of radon-related health issues. Real estate agents (69%) or home inspectors (65%) were the most common sources of information. Respondents were more likely to test their home for radon if they reported previously hearing of radon-related health issues or understanding of how radon-related health issues affect the home-buying process. Respondents in states with notification policies were twice as likely as those without policies to have heard about radon-related health issues (OR 2.01, 95% CI: 1.27-3.17). This study provides useful information for cancer control activities including that education is positively associated with home testing for radon. It also suggests partnering with real estate agents to further radon education and testing efforts to reduce radon exposure and lung cancer risk.

Environmental arsenic exposure: From genetic susceptibility to pathogenesis.

More than 200 million people in 70 countries are exposed to arsenic through drinking water. Chronic exposure to this metalloid has been associated with the onset of many diseases, including cancer. Epidemiological evidence supports its carcinogenic potential, however, detailed molecular mechanisms remain to be elucidated. Despite the global magnitude of this problem, not all individuals face the same risk. Susceptibility to the toxic effects of arsenic is influenced by alterations in genes involved in arsenic metabolism, as well as biological factors, such as age, gender and nutrition. Moreover, chronic arsenic exposure results in several genotoxic and epigenetic alterations tightly associated with the arsenic biotransformation process, resulting in an increased cancer risk. In this review, we: 1) review the roles of inter-individual DNA-level variations influencing the susceptibility to arsenic-induced carcinogenesis; 2) discuss the contribution of arsenic biotransformation to cancer initiation; 3) provide insights into emerging research areas and the challenges in the field; and 4) compile a resource of publicly available arsenic-related DNA-level variations, transcriptome and methylation data. Understanding the molecular mechanisms of arsenic exposure and its subsequent health effects will support efforts to reduce the worldwide health burden and encourage the development of strategies for managing arsenic-related diseases in the era of personalized medicine.

BTEX exposure assessment and quantitative risk assessment among petroleum product distributors.

The aim of this study was to evaluate benzene, toluene, ethylbenzene, and xylene (BTEX) exposure among workers at four stations of a major oil distribution company. Personal BTEX exposure samples were collected over working shift (8h) for 50 workers at four stations of a major oil distribution company in Iran. Measured mean values for workers across four sites were benzene (2437, 992, 584, and 2788µg/m3 respectively), toluene (4415, 2830, 1289, and 9407µg/m3), ethylbenzene (781, 522, 187, and 533µg/m3), and xylene (1134, 678, 322, and 525µg/m3). The maximum mean concentration measured across sites for benzene was 2788µg/m3 (Station 4), toluene was 9407µg/m3 (Station 4), ethylbenzene was 781µg/m3 (Station 1) and xylene was 1134µg/m3 (Station 1). The 8h averaged personal exposure benzene concentration exceeded the recommended value of 1600µg/m3 established by the Iranian Committee for Review and Collection of Occupational Exposure Limit and American Conference of Governmental Industrial Hygienists. Mean values for excess lifetime cancer risk for exposure to benzene were then calculated across workers at each site. Estimates of excess risk ranged from 1.74 ± 4.05 (Station 4) to 8.31 ± 25.81 (Station 3). Risk was assessed by calculation of hazard quotients and hazard indexes, which indicated that xylene and particularly benzene were the strongest contributors. Tanker loading was the highest risk occupation at these facilties. Risk management approaches to reducing exposures to BTEX compounds, especially benzene, will be important to the health of workers in Iran.