Showing papers in "Journal of Environmental Science and Health Part C-environmental Carcinogenesis & Ecotoxicology Reviews in 2014"

Enzyme-like activity of nanomaterials.

Abstract: Due to possessing an extremely small size and a large surface area per unit of volume, nanomaterials have specific characteristic physical, chemical, photochemical, and biological properties that are very useful in many new applications. Nanoparticles' catalytic activity and intrinsic ability in generating or scavenging reactive oxygen species in general can be used to mimic the catalytic activity of natural enzymes. Many nanoparticles with enzyme-like activities have been found, potentially capable of being applied for commercial uses, such as in biosensors, pharmaceutical processes, and the food industry. To date, a variety of nanoparticles, especially those formed from noble metals, have been determined to possess oxidase-like, peroxidase-like, catalase-like, and/or superoxide dismutase-like activity. The ability of nanoparticles to mimic enzymatic activity, especially peroxidase mimics, can be used in a variety of applications, such as detection of glucose in biological samples and waste water treatment. To study the enzyme-like activity of nanoparticles, the electron spin resonance method represents a critically important and convenient analytical approach for zero-time detection of the reactive substrates and products as well as for mechanism determination.

The Toxicological Effects of Halogenated Naphthalenes: A Review of Aryl Hydrocarbon Receptor-Mediated (Dioxin-like) Relative Potency Factors

Abstract: There is no doubt that chloronaphthalenes (PCNs) and their brominated counterparts (PBNs) are dioxin-like compounds, but there is less evidence for mixed bromo/chloronaphthalenes (PXNs). In this article we review information relating to the dioxin-like potency of PCNs and PBNs obtained in vivo, in vitro, and in silico. The aim was to help and improve the quality of data when assessing the contribution of these compounds in the risk analysis of dioxin-like contaminants in foods and other sample types. In vivo and in vitro studies have demonstrated that PCN/PBN congeners are inducers of aryl hydrocarbon hydroxylase, ethoxyresorufin O-deethylase, and luciferase enzymes that are features specifically indicative of planar diaromatic halogenated hydrocarbons such as dioxin and dioxin-like compounds. PCNs in the environment are of multisource origin. The limited data on PBNs in the environment suggest that these also appear to originate from different sources. The toxicological data on these compounds is even scarcer, most of it directed toward explaining the exposure risk from accidental contamination of feed with the commercial PBN containing product, Firemaster BP-6. The occurrence of PBNs and PXNs is possible as ultra-trace environmental and food-chain contaminants produced at least from combustion processes at unknown concentrations. Available toxicological and environmental data enable a focus on PCNs as dioxin analogues to an extent that specific local or regional environmental influences could result in a risk to human health. There is the possibility that they may act synergistically with the better-known classic dioxin and other dioxin-like compounds. PBNs and PXNs are much less studied than the dioxins, but are known to be products of anthropogenic processes that contaminate the environment. A continuously increasing use of bromine for manufacture of brominated flame retardants over the past three decades is anticipated as a stream of "brominated" wastes, that when degraded (combusted), will release PBNs and PXNs. This calls for advanced analytical methods and greater interest toxicologically to understand and control pollution and exposure by PBNs and PXNs. Particular congeners of bromonaphthalene in single studies were found to be much more toxic than their chlorinated counterparts. In addition, brominated/chlorinated naphthalenes also seem to be more potent toxicants than PCNs. About 20% of PCN congeners exhibit a dioxin-like toxicity with relative potencies varying between around 0.003 and 0.000001, but additional and more rigorous data are needed to confirm these figures. Recent food surveys have estimated a small but relevant human exposure to these compounds in foods, giving an additional source of dioxin-like toxicity to those compounds already covered by the World Health Organization-Toxic Equivalency Factors (TEFs) scheme. Given the additivity of response postulated for other dioxin-like compounds, it would seem unwise to ignore this additional contribution. Few data available showed that PBN congeners also exhibit a dioxin-like toxicity and are even more potent than PCN congeners, but the relative potency values were not derived for them until now. There are no toxicological data available for PXNs.

A review of the consequences of global climate change on human health.

Abstract: The impact of climate change has been significant enough to endanger human health both directly and indirectly via heat stress, degraded air quality, rising sea levels, food and water security, extreme weather events (e.g., floods, droughts, earthquakes, volcano eruptions, tsunamis, hurricanes, etc.), vulnerable shelter, and population migration. The deterioration of environmental conditions may facilitate the transmission of diarrhea, vector-borne and infectious diseases, cardiovascular and respiratory illnesses, malnutrition, etc. Indirect effects of climate change such as mental health problems due to stress, loss of homes, economic instability, and forced migration are also unignorably important. Children, the elderly, and communities living in poverty are among the most vulnerable of the harmful effects due to climate change. In this article, we have reviewed the scientific evidence for the human health impact of climate change and analyzed the various diseases in association with changes in the atmospheric environment and climate conditions.

Evaluation of QSAR Models for the Prediction of Ames Genotoxicity: A Retrospective Exercise on the Chemical Substances Registered Under the EU REACH Regulation

Abstract: We evaluated the performance of seven freely available quantitative structure-activity relationship models predicting Ames genotoxicity thanks to a dataset of chemicals that were registered under the EU Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation. The performance of the models was estimated according to Cooper's statistics and Matthew's Correlation Coefficients (MCC). The Benigni/Bossa rule base originally implemented in Toxtree and re-implemented within the Virtual models for property Evaluation of chemicals within a Global Architecture (VEGA) platform displayed the best performance (accuracy = 92%, sensitivity = 83%, specificity = 93%, MCC = 0.68) indicating that this rule base provides a reliable tool for the identification of genotoxic chemicals. Finally, we elaborated a consensus model that outperformed the accuracy of the individual models.

Environmental Exposure to Lead (Pb) and Variations in Its Susceptibility

Abstract: Based on exposure frequency and intrinsic toxicity, lead (Pb) ranks one of the highest priority toxic materials. Continuous regulation of environmental Pb exposure has contributed to dramatically diminished exposure levels of Pb, for example, blood level of Pb. However, the safety level of Pb is not established, as low-level exposure to Pb still shows severe toxicity in high susceptible population and late onset of some diseases from early exposure. In the present study, we focused on food-borne Pb exposure and found broad variations in Pb exposure levels via food among countries. In addition, there are genetic or ethnical variations in Pb-targeted and protective genes. Moreover, various epigenetic alterations were induced by Pb poisoning. Therefore, we suggest a systemic approach including governmental (public) and individual prevention from Pb exposure with continuous biological monitoring and genetic or epigenetic consideration.

Endoplasmic reticulum stress in drug- and environmental toxicant-induced liver toxicity.

Abstract: Liver injury resulting from exposure to drugs and environmental chemicals is a major health problem. Endoplasmic reticulum stress (ER stress) is considered to be an important factor in a wide range of diseases, such as cancer, neurological and cardiovascular disease, diabetes, and inflammatory diseases. The role of ER stress in drug-induced and environmental toxicant-induced liver toxicity has been underestimated in the past; emerging evidence indicates that ER stress makes a substantial contribution to the pathogenesis of drug-induced liver toxicity. In this review, we summarize current knowledge on drugs and environmental toxicants that trigger ER stress in liver and on the underlying molecular mechanisms. We also discuss experimental approaches for ER stress studies.

Epidemiology of Cancers in Serbia and Possible Connection with Cyanobacterial Blooms

Abstract: Cyanobacteria produce toxic metabolites known as cyanotoxins. These bioactive compounds can cause acute poisoning, and some of them may promote cancer through chronic exposure. Direct ingestion of and contact with contaminated water is one of the many exposure routes to cyanotoxins. The aim of this article was to review the incidence of 13 cancers during a 10-year period in Serbia and to assess whether there is a correlation between the cancer incidences and cyanobacterial bloom occurrence in reservoirs for drinking water supply. The types of cancers were chosen and subjected to epidemiological analyses utilizing previously published data. Based on the epidemiological and statistical analysis, the group of districts in which the incidences of cancers are significant, and may be considered as critical, include Nisavski, Toplicki, and Sumadijski district. A significantly higher incidence of ten cancers was observed in the three critical districts as compared to the remaining 14 districts in Central Serbia. These elevated incidences of cancer include: brain cancer, heart, mediastinum and pleura cancer, ovary cancer, testicular cancer, gastric cancer, colorectal cancer, retroperitoneum and peritoneum cancer, leukemia, malignant melanoma of skin, and primary liver cancer. In addition, the mean incidence of five chosen cancers was the highest in the three critical regions, then in the rest of Central Serbia, while the lowest values were recorded in Vojvodina. Persistent and recurrent cyanobacterial blooms occur during summer months in reservoirs supplying water to waterworks in the three critical districts. People in Central Serbia mainly use surface water as water supply (but not all the water bodies are blooming) while in Vojvodina region (control region in this study) only groundwater is used. Among the 14 "noncritical" districts, reservoirs used for drinking water supply have been affected by recurrent cyanobacterial blooms in two districts (Rasinski and Zajecarski), but the waterworks in these districts have been performing ozonation for more than 30 years. We propose that the established statistical differences of cancer incidences in Serbia could be related to drinking water quality, which is affected by cyanobacterial blooms in drinking water reservoirs in certain districts. However, more detailed research is needed regarding cyanobacterial secondary metabolites as risk factors in tumor promotion and cancerogenesis in general.

A review on thiazolidinediones and bladder cancer in human studies.

Abstract: There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of ...

Toxicogenomics and cancer susceptibility: advances with next-generation sequencing.

Abstract: The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual's susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportu...

Chemoprevention Against Arsenic-Induced Mutagenic DNA Breakage and Apoptotic Liver Damage in Rat Via Antioxidant and SOD1 Upregulation by Green Tea (Camellia sinensis) which Recovers Broken DNA Resulted from Arsenic-H2O2 Related in Vitro Oxidant Stress

Abstract: Green tea (Camellia sinensis; CS) strongly reverses/prevents arsenic-induced apoptotic hepatic degeneration/micronecrosis and mutagenic DNA damage in in vitro oxidant stress model and in rat as shown by comet assay and histoarchitecture (HE and PAS staining) results. Earlier, we demonstrated a link between carcinogenesis and impaired antioxidant system-associated mutagenic DNA damage in arsenic-exposed human. In this study, arsenic-induced (0.6 ppm/100 g body weight/day for 28 days) impairment of cytosolic superoxide-dismutase (SOD1), catalase, xanthine-oxidase, thiol, and urate activities/levels led to increase in tissue levels of damaging malondialdehyde, conjugated dienes, serum necrotic-marker lactate-dehydrogenase, and metabolic inflammatory-marker c-reactive protein suggesting dysregulation at the transcriptional/signal-transduction level. These are decisively restrained by CS-extract (≥10 mg/ml aqueous) with a restoration of DNA/tissue structure. The structural/functional impairment of dialyzed and...

Aconitum and delphinium diterpenoid alkaloids of local anesthetic activity: comparative QSAR analysis based on GA-MLRA/PLS and optimal descriptors approach.

Abstract: The duration of anesthesia (related to protein binding of a drug) and the onset time (determined by the pKa) are important characteristics in assessment of local anesthetic agents. They are known to be affected by a number of factors. Early studies of antiarrhythmic diterpenoid alkaloids from plants Aconitum and Delphinium suggested that they possess local anesthetic activity due to their ability to suppress sodium currents of excited membranes. In this study we utilized toxicity, duration, and onset of action as endpoints to construct Quantitative Structure-Activity Relationship (QSAR) models for the series of 34 diterpenoid alkaloids characterized by local anesthetic activity using genetic algorithm-based multiple linear regression analysis/partial least squares and simplified molecular input line entry system (SMILES)-based optimal descriptors approach. The developed QSAR models correctly reflected factors that determine three endpoints of interest. Toxicity correlates with descriptors describing partition and reactivity of compounds. The duration of anesthesia was encoded by the parameters defining the ability of a compound to bind at the receptor site. The size and number of H-bond acceptor atoms were found not to favor the speed of onset, while topographic electronic descriptor demonstrated strong positive effect on it. SMILES-based optimal descriptors approach resulted in overall improvement of models. This approach was shown to be more sensitive to structural peculiarities of molecules than regression methods. The results clearly indicate that obtained QSARs are able to provide distinct rationales for compounds optimization with respect to particular endpoint.

Metabolic Activation of Pyrrolizidine Alkaloids Leading to Phototoxicity and Photogenotoxicity in Human HaCaT Keratinocytes

Abstract: Pyrrolizidine alkaloids, produced by a large number of poisonous plants with wide global distribution, are associated with genotoxicity, tumorigenicity, and hepatotoxicity in animals and humans. Mammalian metabolism converts pyrrolizidine alkaloids to reactive pyrrolic metabolites (dehydropyrrolizidine alkaloids) that form covalent protein and DNA adducts. Although a mechanistic understanding is currently unclear, pyrrolizidine alkaloids can cause secondary (hepatogenous) photosensitization and induce skin cancer. In this study, the phototoxicity of monocrotaline, riddelliine, dehydromonocrotaline, dehydroriddelliine, and dehydroretronecine (DHR) in human HaCaT keratinocytes under ultraviolet A (UVA) irradiation was determined. UVA irradiation of HaCaT cells treated with dehydromonocrotaline, dehydroriddelline, and DHR resulted in increased release of lactate dehydrogenase and enhanced photocytotoxicity proportional to the UVA doses. UVA-induced photochemical DNA damage also increased proportionally with ...

Performance of (Q)SAR Models for Predicting Ames Mutagenicity of Aryl Azo and Benzidine Based Compounds

Abstract: Regulatory agencies worldwide are committed to the objectives of the Strategic Approach to International Chemicals Management to ensure that by 2020 chemicals are used and produced in ways that lead to the minimization of significant adverse effects on human health and the environment. Under the Government of Canada's Chemicals Management Plan, the commitment to address a large number of substances, many with limited data, has highlighted the importance of pursuing alternative hazard assessment methodologies that are able to accommodate chemicals with varying toxicological information. One such method is (Quantitative) Structure Activity Relationships ((Q)SAR) models. The current investigation into the predictivity of 20 (Q)SAR tools designed to model bacterial reverse mutation in Salmonella typhimurium is one of the first of this magnitude to be carried out using an external validation set comprised mainly of industrial chemicals which represent a diverse group of aromatic and benzidine-based azo dyes an...

Rationale and Approaches to the Prevention of Smoking-Related Diseases: Overview of Recent Studies on Chemoprevention of Smoking-Induced Tumors in Rodent Models

Abstract: Tobacco smoke plays a dominant role in the epidemiology of lung cancer, cancer at other sites, and a variety of other chronic diseases. It is the leading cause of death in developed countries, and the global burden of cancer is escalating in less developed regions. For a rational implementation of strategies exploitable for the prevention smoking-related diseases, it is crucial to elucidate both the mechanisms of action of cigarette smoke and the protective mechanisms of the host organism. The imperative primary prevention goal is to avoid any type of exposure to smoke. Epidemiological studies have shown that a decrease in the consumption of cigarettes can be successful in attenuating the epidemic of lung cancer in several countries. Chemoprevention by means of dietary and/or pharmacological agents provides a complementary strategy aimed at decreasing the risk of developing smoking-associated diseases in addicted current smokers, who are unable to quit smoking, and especially in involuntary smokers and ex-smokers. The availability of new animal models that are suitable to detect the carcinogenicity of cigarette smoke and to assess the underlying molecular mechanisms provides new tools for evaluating both safety and efficacy of putative chemopreventive agents.