{"title":"An updated review on cancer risk associated with incretin mimetics and enhancers.","authors":"Chin-Hsiao Tseng, Kuo-Yang Lee, Farn-Hsuan Tseng","doi":"10.1080/10590501.2015.1003496","DOIUrl":"https://doi.org/10.1080/10590501.2015.1003496","url":null,"abstract":"<p><p>Incretin-based therapies, including the use of incretin mimetics of glucagon-like peptide-1 receptor (GLP-1R) agonists and incretin enhancers of dipeptidyl-peptidase 4 (DPP-4) inhibitors, are widely used by clinicians for glucose lowering in patients with type 2 diabetes mellitus. These agents have benefits of a lower risk of hypoglycemia, being neutral for body weight for DPP-4 inhibitors and having a potential for weight reduction with GLP-1R agonists. They may also have a neutral or beneficial cardiovascular effect. Despite these benefits, an increased risk of cancer (especially pancreatic cancer and thyroid cancer) associated with incretin-based therapies has been reported. In this article, we reviewed related literature of experimental animal and observational human studies, clinical trials, and meta-analyses published until December 15, 2014. Current studies suggested a probable role of GLP-1R activation on the development of pancreatic cancer and thyroid cancer in rodents, but such an effect in humans is not remarkable due to the lower or lack of expression of GLP-1R on human pancreatic ductal cells and thyroid tissues. Findings in human studies are controversial and inconclusive. In the analyses of the US Food and Drug Administration adverse events reporting system, a significantly higher risk of pancreatic cancer was observed for GLP-1R agonists and DPP-4 inhibitors, but a significantly higher risk of thyroid cancer was only observed for GLP-1R agonists. Such a higher risk of pancreatic cancer or thyroid cancer could not be similarly demonstrated in other human observational studies or analyses of data from clinical trials. With regards to cancers other than pancreatic cancer and thyroid cancer, available studies supported a neutral association in humans. Some preliminary studies even suggested a potentially beneficial effect on the development of other cancers with the use of incretins. Based on current evidence, continuous monitoring of the cancer issues related to incretin-based therapies is required, even though the benefits may outweigh the potential cancer risk in the general patients with type 2 diabetes mellitus. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 1","pages":"67-124"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1003496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33156319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emilio Benfenati, Serena Manganelli, Sabrina Giordano, Giuseppa Raitano, Alberto Manganaro
{"title":"Hierarchical Rules for Read-Across and In Silico Models of Mutagenicity.","authors":"Emilio Benfenati, Serena Manganelli, Sabrina Giordano, Giuseppa Raitano, Alberto Manganaro","doi":"10.1080/10590501.2015.1096881","DOIUrl":"https://doi.org/10.1080/10590501.2015.1096881","url":null,"abstract":"<p><p>A broad set of rules has been implemented within the ToxRead software for read-across of chemicals for bacterial mutagenicity. These rules were obtained by manually analyzing more than 6000 chemicals and the associated chemical classes. A hierarchy of rules was established to identify those most specifically relating to the target compounds, linked in sequence to the other, more generic ones, which may match with the target compound. Rules related to both mutagenicity and lack of mutagenicity were found. Some of the latter are exceptions to the mutagenicity rules, while others are modulators of activity. These rules can also be used to predict mutagenicity, offering good performance. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 4","pages":"385-403"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1096881","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34032723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gyuri Kim, Ho-Sun Lee, Joon Seok Bang, Boram Kim, Dahae Ko, Mihi Yang
{"title":"A current review for biological monitoring of manganese with exposure, susceptibility, and response biomarkers.","authors":"Gyuri Kim, Ho-Sun Lee, Joon Seok Bang, Boram Kim, Dahae Ko, Mihi Yang","doi":"10.1080/10590501.2015.1030530","DOIUrl":"https://doi.org/10.1080/10590501.2015.1030530","url":null,"abstract":"<p><p>People can be easily exposed to manganese (Mn), the twelfth most abundant element, through various exposure routes. However, overexposure to Mn causes manganism, a motor syndrome similar to Parkinson disease, via interference of the several neurotransmitter systems, particularly the dopaminergic system in areas. At cellular levels, Mn preferentially accumulates in mitochondria and increases the generation of reactive oxygen species, which changes expression and activity of manganoproteins. Many studies have provided invaluable insights into the causes, effects, and mechanisms of the Mn-induced neurotoxicity. To regulate Mn exposure, many countries have performed biological monitoring of Mn with three major biomarkers: exposure, susceptibility, and response biomarkers. In this study, we review current statuses of Mn exposure via various exposure routes including food, high susceptible population, effects of genetic polymorphisms of metabolic enzymes or transporters (CYP2D6, PARK9, SLC30A10, etc.), alterations of the Mn-responsive proteins (i.e., glutamine synthetase, Mn-SOD, metallothioneins, and divalent metal trnsporter1), and epigenetic changes due to the Mn exposure. To minimize the effects of Mn exposure, further biological monitoring of Mn should be done with more sensitive and selective biomarkers. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 2","pages":"229-54"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1030530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33223695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Romualdo Benigni, Chiara Laura Battistelli, Cecilia Bossa, Alessandro Giuliani, Olga Tcheremenskaia
{"title":"Alternative Toxicity Testing: Analyses on Skin Sensitization, ToxCast Phases I and II, and Carcinogenicity Provide Indications on How to Model Mechanisms Linked to Adverse Outcome Pathways.","authors":"Romualdo Benigni, Chiara Laura Battistelli, Cecilia Bossa, Alessandro Giuliani, Olga Tcheremenskaia","doi":"10.1080/10590501.2015.1096885","DOIUrl":"https://doi.org/10.1080/10590501.2015.1096885","url":null,"abstract":"<p><p>This article studies alternative toxicological approaches, with new (skin sensitization, ToxCast) and previous (carcinogenicity) analyses. Quantitative modeling of rate-limiting steps in skin sensitization and carcinogenicity predicts the majority of toxicants. Similarly, successful (Quantitative) Structure-Activity Relationships models exploit the quantification of only one, or few rate-limiting steps. High-throughput assays within ToxCast point to promising associations with endocrine disruption, whereas markers for pathways intermediate events have limited correlation with most endpoints. Since the pathways may be very different (often not simple linear chains of events), quantitative analysis is necessary to identify the type of mechanism and build the appropriate model. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 4","pages":"422-43"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1096885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34028771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tingting Zhao, Tingyao Zhou, Qiuhong Yao, Chunli Hao, Xi Chen
{"title":"Metal nanoclusters: applications in environmental monitoring and cancer therapy.","authors":"Tingting Zhao, Tingyao Zhou, Qiuhong Yao, Chunli Hao, Xi Chen","doi":"10.1080/10590501.2015.1030490","DOIUrl":"https://doi.org/10.1080/10590501.2015.1030490","url":null,"abstract":"<p><p>Metal nanoclusters (NCs), with dimensions between metal atoms and nanoparticles, have attracted more and more attention due to their unique physical and chemical properties. With their size approaching the Fermi wavelength of electrons, metal NCs possess molecule-like properties and excellent fluorescence emission. Owing to their ultrasmall size, strong fluorescence, and excellent biocompatibility, they have been widely studied in environmental and biological fields concerning their applications. In this review, we will introduce the properties of metal NCs, mainly focusing on the synthesis of metal alloy NCs and the recent progress in their applications in environmental monitoring and cancer therapy. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 2","pages":"168-87"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1030490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33218381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protein Mis-Termination Initiates Genetic Diseases, Cancers, and Restricts Bacterial Genome Expansion.","authors":"Tit-Yee Wong, Steve D Schwartzbach","doi":"10.1080/10590501.2015.1053461","DOIUrl":"https://doi.org/10.1080/10590501.2015.1053461","url":null,"abstract":"<p><p>Protein termination is an important cellular process. Protein termination relies on the stop-codons in the mRNA interacting properly with the releasing factors on the ribosome. One third of inherited diseases, including cancers, are associated with the mutation of the stop-codons. Many pathogens and viruses are able to manipulate their stop-codons to express their virulence. The influence of stop-codons is not limited to the primary reading frame of the genes. Stop-codons in the second and third reading frames are referred as premature stop signals (PSC). Stop-codons and PSCs together are collectively referred as stop-signals. The ratios of the stop-signals (referred as translation stop-signals ratio or TSSR) of genetically related bacteria, despite their great differences in gene contents, are much alike. This nearly identical Genomic-TSSR value of genetically related bacteria may suggest that bacterial genome expansion is limited by their unique stop-signals bias. We review the protein termination process and the different types of stop-codon mutation in plants, animals, microbes, and viruses, with special emphasis on the role of PSCs in directing bacterial evolution in their natural environments. Knowing the limit of genomic boundary could facilitate the formulation of new strategies in controlling the spread of diseases and combat antibiotic-resistant bacteria. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 3","pages":"255-85"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1053461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33399965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianqing Ruan, Hong Gao, Na Li, Junyi Xue, Jie Chen, Changqiang Ke, Yang Ye, Peter Pi-Cheng Fu, Jiang Zheng, Jiyao Wang, Ge Lin
{"title":"Blood Pyrrole-Protein Adducts--A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans.","authors":"Jianqing Ruan, Hong Gao, Na Li, Junyi Xue, Jie Chen, Changqiang Ke, Yang Ye, Peter Pi-Cheng Fu, Jiang Zheng, Jiyao Wang, Ge Lin","doi":"10.1080/10590501.2015.1096882","DOIUrl":"https://doi.org/10.1080/10590501.2015.1096882","url":null,"abstract":"<p><p>Pyrrolizidine alkaloids (PAs) induce liver injury (PA-ILI) and is very likely to contribute significantly to drug-induced liver injury (DILI). In this study we used a newly developed ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry (UHPLC-MS)-based method to detect and quantitate blood pyrrole-protein adducts in DILI patients. Among the 46 suspected DILI patients, 15 were identified as PA-ILI by the identification of PA-containing herbs exposed. Blood pyrrole-protein adducts were detected in all PA-ILI patients (100%). These results confirm that PA-ILI is one of the major causes of DILI and that blood pyrrole-protein adducts quantitated by the newly developed UHPLC-MS method can serve as a specific biomarker of PA-ILI. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 4","pages":"404-21"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1096882","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34029270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transformation assay in Bhas 42 cells: a model using initiated cells to study mechanisms of carcinogenesis and predict carcinogenic potential of chemicals.","authors":"Kiyoshi Sasaki, Makoto Umeda, Ayako Sakai, Shojiro Yamazaki, Noriho Tanaka","doi":"10.1080/10590501.2014.967058","DOIUrl":"https://doi.org/10.1080/10590501.2014.967058","url":null,"abstract":"<p><p>Transformation assays using cultured cells have been applied to the study of carcinogenesis. Although various cell systems exist, few cell types such as BALB/c 3T3 subclones and Syrian hamster embryo cells have been used to study chemically induced two-stage carcinogenesis. Bhas 42 cells were established as a clone by the transfection with the v-Ha-ras gene into mouse BALB/c 3T3 A31-1-1 cells and their subsequent selection based on their sensitivity to 12-O-tetradecanoylphorbol-13-acetate. Using Bhas 42 cells, transformed foci were induced by the treatment with nongenotoxic carcinogens, most of which act as tumor promoters. Therefore, Bhas 42 cells were considered to be a model of initiated cells. Subsequently, not only nongenotoxic carcinogens but also genotoxic carcinogens, most of which act as tumor initiators, were found to induce transformed foci by the modification of the protocol. Furthermore, transformation of Bhas 42 cells was induced by the transfection with genes of oncogenic potential. We interpret this high sensitivity of Bhas 42 cells to various types of carcinogenic stimuli to be related to the multistage model of carcinogenesis, as the transfection of v-Ha-ras gene further advances the parental BALB/c 3T3 A31-1-1 cells toward higher transforming potential. Thus, we propose that Bhas 42 cells are a novel and sensitive cell line for the analysis of carcinogenesis and can be used for the detection of not only carcinogenic substances but also gene alterations related to oncogenesis. This review will address characteristics of Bhas 42 cells, the transformation assay protocol, validation studies, and the various chemicals tested in this assay. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 1","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2014.967058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33156317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zorica Svirčev, Jelena Lujić, Zoran Marinović, Damjana Drobac, Nada Tokodi, Bratislav Stojiljković, Jussi Meriluoto
{"title":"Toxicopathology induced by microcystins and nodularin: a histopathological review.","authors":"Zorica Svirčev, Jelena Lujić, Zoran Marinović, Damjana Drobac, Nada Tokodi, Bratislav Stojiljković, Jussi Meriluoto","doi":"10.1080/10590501.2015.1003000","DOIUrl":"https://doi.org/10.1080/10590501.2015.1003000","url":null,"abstract":"<p><p>Cyanobacteria are present in all aquatic ecosystems throughout the world. They are able to produce toxic secondary metabolites, and microcystins are those most frequently found. Research has displayed a negative influence of microcystins and closely related nodularin on fish, and various histopathological alterations have been observed in many organs of the exposed fish. The aim of this article is to summarize the present knowledge of the impact of microcystins and nodularin on the histology of fish. The observed negative effects of cyanotoxins indicate that cyanobacteria and their toxins are a relevant medical (due to irritation, acute poisoning, tumor promotion, and carcinogenesis), ecotoxicological, and economic problem that may affect both fish and fish consumers including humans. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 2","pages":"125-67"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1003000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33218380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular fingerprints of environmental carcinogens in human cancer.","authors":"C Ceccaroli, A Pulliero, M Geretto, A Izzotti","doi":"10.1080/10590501.2015.1030491","DOIUrl":"https://doi.org/10.1080/10590501.2015.1030491","url":null,"abstract":"<p><p>Identification of specific molecular changes (fingerprints) is important to identify cancer etiology. Exploitable biomarkers are related to DNA, epigenetics, and proteins. DNA adducts are the turning point between environmental exposures and biological damage. DNA mutational fingerprints are induced by carcinogens in tumor suppressor and oncogenes. In an epigenetic domain, methylation changes occurs in specific genes for arsenic, benzene, chromium, and cigarette smoke. Alteration of specific microRNA has been reported for environmental carcinogens. Benzo(a)pyrene, cadmium, coal, and wood dust hits specific heat-shock proteins and metalloproteases. The multiple analysis of these biomarkers provides information on the carcinogenic mechanisms activated by exposure to environmental carcinogens. </p>","PeriodicalId":51085,"journal":{"name":"Journal of Environmental Science and Health Part C-Environmental Carcinogenesis & Ecotoxicology Reviews","volume":"33 2","pages":"188-228"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10590501.2015.1030491","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33218382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}