Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews最新文献

Urinary tract tumors are tenth in frequency, and many environmental carcinogens are excreted by urine. Interplay between chronic inflammatory urolithiasis and urothelial carcinogenesis is not well understood. Experimental evidences show that dietary melamine induce these events even at low concentrations. This is important because thousands of children were exposed to melamine through intentionally contaminated milk formula worldwide. We propose that an increased risk for urinary tumors in adult life may occur and screenings for early urinary signs may be necessary. Therefore, urothelial biology, melamine carcinogenic potential, and related epidemiology are discussed, recommending a preventive dietary polyunsaturated fatty acid-based supplementation, since they modulate such interplay in rodents.

The globally escalating thyroid nodule incidence rates may be only partially ascribed to better diagnostics, allowing for the assessment of environmental risk factors on thyroid disease. Endocrine disruptors or thyroid-disrupting chemicals (TDC) like bisphenol A, phthalates, and polybrominated diphenyl ethers are widely used as plastic additives in consumer products. This comprehensive review studied the magnitude and uncertainty of TDC exposures and their effects on thyroid hormones for sensitive subpopulation groups like pregnant women, infants, and children. Our findings qualitatively suggest the mixed, significant (α = 0.05) TDC associations with natural thyroid hormones (positive or negative sign). Future studies should undertake systematic meta-analyses to elucidate pooled TDC effect estimates on thyroid health indicators and outcomes.

This systematic investigation examines gas transport in the lung for two sets of chlorohydrocarbons (CHCs): the chloromethanes (C1) and chloroethanes (C2). The C1 series includes chloromethane, methylene chloride, chloroform, and carbon tetrachloride, and the C2 series includes chloroethane, 1,2-dichloroethane, 1, 1, 2-trichloroethane, and 1, 1, 2, 2-tetrachloroethane. Most CHC gases cause narcosis. The comprehensive narcosis work of Lehmann and colleagues on CHCs was used as a basis for the narcosis endpoint in the present examination. The sites for narcosis are located in the brain (midline cortex and posterior parietal area), the spine, and at many peripheral nerve sites. Central nervous system (CNS) exposure executes a multisite, neural transmission set of inhibitions that promotes rapid loss of consciousness, sensory feeling, and current and stored memory while providing temporary amnesia. Absorption into the system requires dissolution into many lipid membranes and binding to lipoproteins. Lipophilicity is a CHC property shared with many anesthetics according to the Meyer-Overton Rule. Many structurally different lipid chemicals produce the narcosis response when the lipid concentration exceeds -67 mM. This suggests narcotic or anesthetic dissolution into CNS membranes until the lipid organization is disrupted or perturbed. This perturbation includes loading of Na(+)- and K(+)-channel transmembrane lipoprotein complexes and disrupting their respective channel functional organizations. The channel functions become attenuated or abrogated until the CHC exposure ceases and CHC loading reverses. This investigation demonstrates how the CHC physical and chemical properties influence the absorption of these CHCs via the lung and the alveolar system on route to the blood. Narcosis in test animals was used here as an objective biological endpoint to study the effects of the physical factors Bp, Vp, Kd (oil: gas) partition, Henry's constant (HK), and water solubility (S%) on gas transport. Narcosis is immediate after gas exposure and requires no chemical activation only absorption into the blood and circulation to CNS narcotic sites. The three physical factors Bp, K(d) (oil: air), and S% vary directly with unitary narcosis (UN) whereas Vp and HK vary inversely with UN in linear log-log relationships for the C2 series but not for the C1 series. Physicochemical properties of C1 series gases indicate why they depart from what is usually assumed to be an Ideal Gas. An essential discriminating process in the distal lung is the limiting alveolar film layer (AFL) and the membrane layer of the alveolar acini. The AFL step influences gas uptake by physically limiting the absorption process. Interaction with and dissolution into aqueous solvent of the AFL is required for transport and narcotic activity. Narcotics or anesthetics must engage the aqueous AFL with sufficient strength to allow transport and absorption for downstream CNS binding. CHCs that do

Modern approaches in health care are moving toward the model of "personalized medicine." Today, current research in molecular biology and medicine is focused on developing genomic markers with predictive, therapeutic, and prognostic significance. One of the most widespread and significant genomic markers is the single nucleotide polymorphism (SNP), which represents a variation in DNA sequence when a single nucleotide differs between members of a biological species or paired chromosomes in an individual. Antioxidant defense enzymes break down dangerous reactive compounds, called reactive oxygen species, and prevent DNA strand from carcinogen-specific mutations. It is well known that inherited variations in genes that encode antioxidant defense enzymes may modulate individual susceptibility to cancer. In our previous study we have determined the predictive significance of several SNPs of superoxide dismutase (SOD) and glutathione peroxidase gene families in the context of cancer risk. The present review includes a summary and discussion of the current findings evaluating the role of SNPs of the myeloperoxidase (MPO) and paraoxanase (PON) genes in cancer occurrence and development. We suggest that rs2333227 (MPO_ -463G/A) and rs854560 polymorphisms have a great predictive significance; they could probably be utilized as cancer predictors in the future. Also, we recommend further in-depth research for rs11079344 (MPO), rs8178406 (MPO), rs2243828 (MPO), rs662 (PON1), rs705379 (PON1), and PON1_304A/G polymorphisms. These SNPs may become significant cancer-associated biomarkers.

Epigenetics has been emphasized in the postgenome era to clarify obscure health risks of environmental toxicants including endocrine disrupting chemicals (EDCs). In addition, mixed exposure in real life can modify health consequences of the toxicants. Particularly, some nutritional and dietary materials modify individual susceptibility through changes in the epigenome. Therefore, we focused on some environmental toxicants that induce epigenetic alterations, and introduced chemopreventive materials to reverse the toxicants-induced epigenetic alterations. Methodologically, we used global and specific DNA methylation as epigenetic end points and searched epigenetic modulators in food. We reviewed various epigenetic end points induced by environmental toxicants including alcohol, asbestos, nanomaterials, benzene, EDCs, metals, and ionizing radiation. The epigenetic end points can be summarized into global hypomethylation and specific hypermethylation at diverse tumor suppress genes. Exposure timing, dose, sex, or organ specificity should be considered to use the epigenetic end points as biomarkers for exposure to the epimutagenic toxicants. Particularly, neonatal exposure to the epimutagens can influence their future adult health because of characteristics of the epimutagens, which disrupt epigenetic regulation in imprinting, organogenesis, development, etc. Considering interaction between epimutagenic toxicants and their reversers in food, we suggest that multiple exposures to them can alleviate or mask epigenetic toxicity in real life. Our present review provides useful information to find new end points of environmental toxicants and to prevention from environment-related diseases.

Asbestos is now banned in 52 countries. Although Italy banned asbestos in 1992, up until that date it had been one of the main producer nations of asbestos and asbestos-containing materials, and asbestos-related contamination is still widespread in the country. To reduce asbestos-related health effects, Italy has adopted many laws and regulations regarding exposure thresholds and remediation tools. Even so, there are legislative gaps that are making it difficult to manage related risks especially in the operative phase. The lack of standard procedures at a national level regarding emergency shutdown and remediation as well as reference thresholds for specific risk situations creates difficulties and different actions when dealing with the cleanup of Italian asbestos superfund sites. The authors propose operative guidelines for asbestos remediation at Italian superfund sites. INAIL, the reference national organization for asbestos-related matters, acting as an advisor to a number of state, regional, and local authorities, examined the main asbestos-related risk situations in Italy and proposed the most appropriate actions to take. The detailed analysis of many actual cases of risk, in part through inspections and the management of cleanup actions at asbestos Italian superfund sites, resulted in proposals to modify existing procedures and thresholds, which were subsequently discussed with all national, regional, and local scientific bodies. After more than two years of work and discussion at a national level, INAIL-DIPIA-Asbestos Group drafted new Guidelines for Asbestos Remediation at Italian Superfund sites, and officially submitted them to the Environment Ministry. The Ministry then adopted the document in regard to all asbestos Italian superfunds. This recently released document is also a useful reference for contaminated sites at a regional and local level. The operative Guidelines for Asbestos Remediation at Italian Superfund sites may also be of use at an international level for countries that have already banned asbestos and are engaged in remediation activity and for countries that have not yet banned asbestos but wish to adopt risk prevention measures.

Polycyclic aromatic hydrocarbons (PAHs) are a class of mutagenic and tumorigenic environmental contaminants. Although the mechanisms by which PAHs induce cancer in experimental animals have been extensively studied and the metabolic activation pathways have been determined, the environmental fate of PAHs and the phototoxicity exerted by PAHs, as well as their photoreaction products formed in the environment, have received much less attention. In this review, the formation of oxygenated PAHs, PAH quinones, nitro-PAHs, and halogenated PAHs from photoreaction of environmental PAHs are addressed. Upon light irradiation, PAHs and all PAH photoreaction products can absorb light energy to reach photo-excited states, which react with molecular oxygen, medium, and coexisting chemicals to produce reactive oxygen species (ROS) and other reactive intermediates, such as oxygenated PAHs and free radicals. These intermediates, including ROS, induce lipid peroxidation, and DNA damage including DNA strand breakage, oxidation to 8-oxo-2'-deoxyguanosine, and DNA-adducts. Since these toxicological endpoints are associated with age-related diseases, including cancer, environmental PAHs concomitantly exposed to sunlight may potentially promote human skin damage, leading to ageing and skin cancers. Thus, we suggest that (i) in addition to the widely recognized metabolic pathways, more attention must be paid to photoreaction as an important activation pathway for PAHs, (ii) risk assessment of environmental PAHs should take into consideration the complex photochemical reactions leading to mixtures of products that are also phototoxic; and (iii) the study of structure-toxicity relationships should be expanded to cover the complex photoreactions and extrinsic factors that affect phototoxicity endpoints.

During the past half-century, incidences of breast cancer have increased globally. Various factors--genetic and environmental--have been implicated in the initiation and progression of this disease. One potential environmental risk factor that has not received a lot of attention is the exposure to heavy metals. While several mechanisms have been put forth describing how high concentrations of heavy metals play a role in carcinogenesis, it is unclear whether chronic, low-level exposure to certain heavy metals (i.e., cadmium and nickel) can directly result in the development and progression of cancer. Cadmium and nickel have been hypothesized to play a role in breast cancer development by acting as metalloestrogens--metals that bind to estrogen receptors and mimic the actions of estrogen. Since the lifetime exposure to estrogen is a well-established risk factor for breast cancer, anything that mimics its activity will likely contribute to the etiology of the disease. However, heavy metals, depending on their concentration, are capable of binding to a variety of proteins and may exert their toxicities by disrupting multiple cellular functions, complicating the analysis of whether heavy metal-induced carcinogenesis is mediated by the estrogen receptor. The purpose of this review is to discuss the various epidemiological, in vivo, and in vitro studies that show a link between the heavy metals, cadmium and nickel, and breast cancer development. We will particularly focus on the studies that test whether these two metals act as metalloestrogens in order to assess the strength of the data supporting this hypothesis.

This article reviews available animal studies on the possible link between the use of peroxisome proliferator-activated receptor (PPAR) agonists and bladder cancer, with further discussion on the possible implications to humans. Carcinogenicity studies suggest that the PPARγ agonist pioglitazone and dual PPARα/γ agonists such as ragaglitazar, muraglitazar, and naveglitazar may increase the risk of bladder cancer in a dose-responsive pattern in rats. It is interesting that bladder cancer related to PPAR agonists shows remarkable species- and sex-specificity and has a predilection to occur in the ventral dome of bladder in rodents. While male rats treated with pioglitazone or muraglitazar have a higher propensity to develop bladder cancer than female rats, mice of both sexes do not develop bladder cancer even when exposed to very high doses. Direct genotoxicity or cytotoxicity of PPAR agonists is unlikely to be the mode of action because most of the parent compounds or their metabolites of the PPAR agonists are neither mutagenic nor genotoxic, and they are rarely excreted in the urine; but a receptor-mediated PPAR effect cannot be excluded. Some suggest a "urolithiasis hypothesis" referring to the formation of urinary solids and calculi, which subsequently causes bladder necrosis, regenerative proliferation, hypertrophy, and cancer. However, whether these animal findings could have human relevance is not yet fully understood. Some argue that the urolithiasis-induced bladder cancer might be rat-specific and would probably not be applicable to humans. An effect of increased urinary growth factors induced by PPAR agonists has also been proposed, but this requires more investigations. Before fully clarified, a balance between the risks and benefits of the use of pioglitazone, an approved oral antidiabetic agent that has recently been linked to an increased but not yet confirmed risk of bladder cancer in humans, should be justified for individual use.