Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.75420
D. Želježić
Already in 1978, Elisabeth C. Miller and James A. Miller came with a presumption that electrophilic molecules are predicted to be carcinogens. It is because DNA molecule is reached in nucleophilic centres that may covalently bind to such substances. Rules deduced by Millers are even nowadays irrefutable, and they are used as the basis of testing of the substance for its carcinogenicity potential. Toxicological discipline that emerged from Millers’ research is based on dependence of chemical structure of the substance and their biological activity. Even further, there are strict regularities between molecular structures and activities. The tool used in assessment of biological activity of a substance is known as SAR, an abbreviation from structure–activity relationship. Besides electrophilic centres, in assessment of carcinogenic potential of a substance, the SAR also encounters chemical surrounding (neighbouring functional groups), size of the substance, its lipophilicity, number and position of aryl rings, substitutions of hydrogens, epoxides in aliphatic moieties or rings, resonance stabilisation, etc. To these days, SAR has been upgraded to quantitative SAR (QSAR) which applies multivariate statistical methods quantitatively comparing detected characteristics of “alerts” with biological activity of known carcinogens. Nowadays, chemical industry developing novel active substances is unthinkable without application of QSAR.
早在1978年，伊丽莎白·c·米勒(Elisabeth C. Miller)和詹姆斯·a·米勒(James a . Miller)就提出了一个假设，即亲电分子被预测为致癌物。这是因为DNA分子到达亲核中心，可以与这些物质共价结合。即使在今天，米勒推断出的规则也是无可辩驳的，这些规则被用作测试物质致癌性的基础。从米勒的研究中产生的毒理学学科是基于物质的化学结构及其生物活性的依赖性。更进一步说，分子结构和活动之间有严格的规律。用于评估物质生物活性的工具称为SAR，是构效关系的缩写。除了亲电中心，在评估一种物质的致癌潜力时，SAR还会遇到化学周围(邻近的官能团)、物质的大小、亲脂性、芳基环的数量和位置、氢的取代、脂肪族部分或环中的环氧化物、共振稳定性等。到目前为止，SAR已升级为定量SAR (QSAR)，即应用多元统计方法定量比较“警报”检测到的特征与已知致癌物的生物活性。如今，化学工业开发新的活性物质离不开QSAR的应用。
{"title":"Assessment of Potential Carcinogenicity by Quantitative Structure-Activity Relationship (QSAR)","authors":"D. Želježić","doi":"10.5772/INTECHOPEN.75420","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75420","url":null,"abstract":"Already in 1978, Elisabeth C. Miller and James A. Miller came with a presumption that electrophilic molecules are predicted to be carcinogens. It is because DNA molecule is reached in nucleophilic centres that may covalently bind to such substances. Rules deduced by Millers are even nowadays irrefutable, and they are used as the basis of testing of the substance for its carcinogenicity potential. Toxicological discipline that emerged from Millers’ research is based on dependence of chemical structure of the substance and their biological activity. Even further, there are strict regularities between molecular structures and activities. The tool used in assessment of biological activity of a substance is known as SAR, an abbreviation from structure–activity relationship. Besides electrophilic centres, in assessment of carcinogenic potential of a substance, the SAR also encounters chemical surrounding (neighbouring functional groups), size of the substance, its lipophilicity, number and position of aryl rings, substitutions of hydrogens, epoxides in aliphatic moieties or rings, resonance stabilisation, etc. To these days, SAR has been upgraded to quantitative SAR (QSAR) which applies multivariate statistical methods quantitatively comparing detected characteristics of “alerts” with biological activity of known carcinogens. Nowadays, chemical industry developing novel active substances is unthinkable without application of QSAR.","PeriodicalId":106608,"journal":{"name":"Genotoxicity - A Predictable Risk to Our Actual World","volume":"72 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125222797","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}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.77968
D. Aiassa
The importance of early detection of genetic damage is that it allows taking the necessary measures to reduce or suppress the exposure to the deleterious agent when it is still reversible, thus decreasing the risk of developing diseases. For this reason, genotoxicity tests should be considered as indispensable tools in the implementation of a complete medical surveillance in people potentially exposed to various environmental pollutants and especially those who live in the same place with people who have already developed some type of neoplasia at early ages in order to prevent the occurrence of tumors of environmental origin and work-related. On the other hand, the application of these tests is useful to detect possible long-term effects of substances that are introduced to the market without knowing exactly their capacity to affect human and environmental health.
{"title":"Genotoxic Risk in Human Populations Exposed to Pesticides","authors":"D. Aiassa","doi":"10.5772/INTECHOPEN.77968","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77968","url":null,"abstract":"The importance of early detection of genetic damage is that it allows taking the necessary measures to reduce or suppress the exposure to the deleterious agent when it is still reversible, thus decreasing the risk of developing diseases. For this reason, genotoxicity tests should be considered as indispensable tools in the implementation of a complete medical surveillance in people potentially exposed to various environmental pollutants and especially those who live in the same place with people who have already developed some type of neoplasia at early ages in order to prevent the occurrence of tumors of environmental origin and work-related. On the other hand, the application of these tests is useful to detect possible long-term effects of substances that are introduced to the market without knowing exactly their capacity to affect human and environmental health.","PeriodicalId":106608,"journal":{"name":"Genotoxicity - A Predictable Risk to Our Actual World","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131187153","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}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.74128
J. Heredia-Rojas, R. Gomez-flores, Eulogio De laCruz-Torres, Omar Heredia-Rodríguez, E. Campos-Góngora, P. C. Cantú-Martínez, Laura E. Rodríguez-Flores, A. O. Fuente
Modern life implies a constant exposure of living organisms to many sources of radiation, especially electromagnetic fields (EMFs) generated by our technological devices. The question of whether or not EMFs in the non-ionizing extremely low frequency (ELF) range can induce genotoxic effects is currently a subject of interest. People of industrialized societies are commonly exposed to EMFs and waves in a very broad range of frequencies, including power lines, telecommunications, and domestic and industrial equipment. In this review, we present controversial evidence from our research group and others of genotoxicity induced by ELF-EMFs, since scientific community consider EMF devices produce marginal amounts of energy, which does not justify any DNA alterations, together with conflicting laboratory results and few epidemiological studies. However, in 2002 the International Agency for Research on Cancer (IARC) categorized ELF-EMFs as being potential carcinogenic and genotoxic agents to humans. The aim of the present chapter is to discuss the role of ELM-EMFs on human genotoxicity.
{"title":"Genotoxicity by Electromagnetic Fields","authors":"J. Heredia-Rojas, R. Gomez-flores, Eulogio De laCruz-Torres, Omar Heredia-Rodríguez, E. Campos-Góngora, P. C. Cantú-Martínez, Laura E. Rodríguez-Flores, A. O. Fuente","doi":"10.5772/INTECHOPEN.74128","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.74128","url":null,"abstract":"Modern life implies a constant exposure of living organisms to many sources of radiation, especially electromagnetic fields (EMFs) generated by our technological devices. The question of whether or not EMFs in the non-ionizing extremely low frequency (ELF) range can induce genotoxic effects is currently a subject of interest. People of industrialized societies are commonly exposed to EMFs and waves in a very broad range of frequencies, including power lines, telecommunications, and domestic and industrial equipment. In this review, we present controversial evidence from our research group and others of genotoxicity induced by ELF-EMFs, since scientific community consider EMF devices produce marginal amounts of energy, which does not justify any DNA alterations, together with conflicting laboratory results and few epidemiological studies. However, in 2002 the International Agency for Research on Cancer (IARC) categorized ELF-EMFs as being potential carcinogenic and genotoxic agents to humans. The aim of the present chapter is to discuss the role of ELM-EMFs on human genotoxicity.","PeriodicalId":106608,"journal":{"name":"Genotoxicity - A Predictable Risk to Our Actual World","volume":"116 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123171680","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}
Pub Date : 2017-12-20DOI: 10.5772/INTECHOPEN.71923
Özlem Sultan Aslantürk
Cytotoxicity is one of the most important indicators for biological evaluation in vitro studies. In vitro, chemicals such as drugs and pesticides have different cytotoxicity mechanisms such as destruction of cell membranes, prevention of protein synthesis, irreversible binding to receptors etc. In order to determine the cell death caused by these damages, there is a need for cheap, reliable and reproducible short-term cytotoxicity and cell viability assays. Cytotoxicity and cell viability assays are based on various cell functions. A broad spectrum of cytotoxicity assays is currently used in the fields of toxicology and pharmacology. There are different classifications for these assays: (i) dye exclusion assays; (ii) colorimetric assays; (iii) fluorometric assays; and (iv) luminometric assays. Choosing the appropriate method among these assays is important for obtaining accurate and reliable results. When selecting the cytotoxicity and cell viability assays to be used in the study, different parameters have to be considered such as the availability in the laboratory where the study is to be performed, test compounds, detection mechanism, specificity, and sensitivity. In this chapter, information will be given about in vitro cytotoxicity and viability assays, these assays will be classified and their advantages and disadvantages will be emphasized. The aim of this chapter is to guide the researcher interested in this subject to select the appropriate assay for their study.
{"title":"In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages","authors":"Özlem Sultan Aslantürk","doi":"10.5772/INTECHOPEN.71923","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.71923","url":null,"abstract":"Cytotoxicity is one of the most important indicators for biological evaluation in vitro studies. In vitro, chemicals such as drugs and pesticides have different cytotoxicity mechanisms such as destruction of cell membranes, prevention of protein synthesis, irreversible binding to receptors etc. In order to determine the cell death caused by these damages, there is a need for cheap, reliable and reproducible short-term cytotoxicity and cell viability assays. Cytotoxicity and cell viability assays are based on various cell functions. A broad spectrum of cytotoxicity assays is currently used in the fields of toxicology and pharmacology. There are different classifications for these assays: (i) dye exclusion assays; (ii) colorimetric assays; (iii) fluorometric assays; and (iv) luminometric assays. Choosing the appropriate method among these assays is important for obtaining accurate and reliable results. When selecting the cytotoxicity and cell viability assays to be used in the study, different parameters have to be considered such as the availability in the laboratory where the study is to be performed, test compounds, detection mechanism, specificity, and sensitivity. In this chapter, information will be given about in vitro cytotoxicity and viability assays, these assays will be classified and their advantages and disadvantages will be emphasized. The aim of this chapter is to guide the researcher interested in this subject to select the appropriate assay for their study.","PeriodicalId":106608,"journal":{"name":"Genotoxicity - A Predictable Risk to Our Actual World","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114939313","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}
Pub Date : 2017-12-20DOI: 10.5772/INTECHOPEN.71319
S. Coimbra, A. Santos-Silva, E. Costa, E. Bronze-da-Rocha
Inflammation is a common feature in end stage renal disease (ESRD) that might contribute to increase DNA damage. ESRD patients present increased circulating cell-free DNA (cfDNA) and different types of DNA injury. The underlying inflammatory process in ESRD may be associated with increased genomic damage and cfDNA contributing to further enhance inflammation. We analyzed the degree of genomic damage in ESRD patients under hemodialysis therapy, using the comet assay and cfDNA quantification. ESRD patients presented significantly higher C-reactive protein (CRP) and cell damaged DNA. The cfDNA correlated with age and inflammatory stage. Nine out of 39 patients died during the one year follow-up period and presented significantly higher cfDNA, than those who persisted alive. At lower CRP values, the increased DNA damage is still within the cell, and at higher CRP the damaged DNA is released in to plasma. The higher degree of genomic damage in ESRD might be a consequence of inflammation and aging, and may contribute to increase cancer and cardiovascular mortality risk. Our data suggest that the comet assay is more sensitive for low-grade inflammatory conditions, while cfDNA appears as a good biomarker for more severe inflammatory conditions, and as a biomarker for the outcome of ESRD patients.
{"title":"DNA Damage in End-Stage Renal Disease Patients. Assessment by In Vitro Comet Assay and by Cell-Free DNA Quantification","authors":"S. Coimbra, A. Santos-Silva, E. Costa, E. Bronze-da-Rocha","doi":"10.5772/INTECHOPEN.71319","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.71319","url":null,"abstract":"Inflammation is a common feature in end stage renal disease (ESRD) that might contribute to increase DNA damage. ESRD patients present increased circulating cell-free DNA (cfDNA) and different types of DNA injury. The underlying inflammatory process in ESRD may be associated with increased genomic damage and cfDNA contributing to further enhance inflammation. We analyzed the degree of genomic damage in ESRD patients under hemodialysis therapy, using the comet assay and cfDNA quantification. ESRD patients presented significantly higher C-reactive protein (CRP) and cell damaged DNA. The cfDNA correlated with age and inflammatory stage. Nine out of 39 patients died during the one year follow-up period and presented significantly higher cfDNA, than those who persisted alive. At lower CRP values, the increased DNA damage is still within the cell, and at higher CRP the damaged DNA is released in to plasma. The higher degree of genomic damage in ESRD might be a consequence of inflammation and aging, and may contribute to increase cancer and cardiovascular mortality risk. Our data suggest that the comet assay is more sensitive for low-grade inflammatory conditions, while cfDNA appears as a good biomarker for more severe inflammatory conditions, and as a biomarker for the outcome of ESRD patients.","PeriodicalId":106608,"journal":{"name":"Genotoxicity - A Predictable Risk to Our Actual World","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129147194","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}
Pub Date : 2017-12-20DOI: 10.5772/INTECHOPEN.72434
E. Paravani, V. Casco
Cypermethrin (Cyp), is one of the most common contaminants in freshwater aquatic systems. We evaluated its possible genotoxic effect and oxidative stress in retinal cells of adult zebrafish exposed to 0.3 μg/L and 0.6 μg/L Cyp. Both the histological and immunofluorescence (IF) techniques showed the presence of apoptotic cells in the zebrafish retina after 9 days of treatment with 0.6 μg/L Cyp. Thus, histone γ-H2AX, a double-stranded DNA damage marker, was immunodetected in both the outer and inner nuclear layer after exposure to 0.6 μg/L Cyp for 12 days, while the anti-cas- pase-3 apoptotic antibody was detected in the outer nuclear layer. Compared with the morphological evidence, the damage index (DI) showed significant differences with 0.3 μg/L from day 9, while with 0.6 μg/L all the stages evaluated showed very significant differences. According to these results, it was verified that the activities of superoxide dismutase (SOD) and catalase (CAT) increased significantly after exposure to 0.6 μg/L Cyp. The same treatment caused a significant positive regulation of the mRNA levels of both genes. These results indicate that Cyp causes DNA damage and oxidative stress. This pyrethroid also has the potential to induce apoptosis in the cells of the retina. neurotoxicity but also suggest that zebrafish can serve as an ideal model for studying developmental toxicity of environmental contaminants.
{"title":"Genotoxicity Induced by Cypermethrin in the Zebrafish Retina","authors":"E. Paravani, V. Casco","doi":"10.5772/INTECHOPEN.72434","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72434","url":null,"abstract":"Cypermethrin (Cyp), is one of the most common contaminants in freshwater aquatic systems. We evaluated its possible genotoxic effect and oxidative stress in retinal cells of adult zebrafish exposed to 0.3 μg/L and 0.6 μg/L Cyp. Both the histological and immunofluorescence (IF) techniques showed the presence of apoptotic cells in the zebrafish retina after 9 days of treatment with 0.6 μg/L Cyp. Thus, histone γ-H2AX, a double-stranded DNA damage marker, was immunodetected in both the outer and inner nuclear layer after exposure to 0.6 μg/L Cyp for 12 days, while the anti-cas- pase-3 apoptotic antibody was detected in the outer nuclear layer. Compared with the morphological evidence, the damage index (DI) showed significant differences with 0.3 μg/L from day 9, while with 0.6 μg/L all the stages evaluated showed very significant differences. According to these results, it was verified that the activities of superoxide dismutase (SOD) and catalase (CAT) increased significantly after exposure to 0.6 μg/L Cyp. The same treatment caused a significant positive regulation of the mRNA levels of both genes. These results indicate that Cyp causes DNA damage and oxidative stress. This pyrethroid also has the potential to induce apoptosis in the cells of the retina. neurotoxicity but also suggest that zebrafish can serve as an ideal model for studying developmental toxicity of environmental contaminants.","PeriodicalId":106608,"journal":{"name":"Genotoxicity - A Predictable Risk to Our Actual World","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131561374","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}
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