Pub Date : 2020-10-07DOI: 10.5772/intechopen.93702
A. Zhgun
A filamentous fungus (also called molds or moldy fungus) is a taxonomically diverse organism from phylum Zygomycota and Ascomycota with filamentous hyphae and has the ability to produce airborne spores or conidia. Currently, more than 70,000 molds are known, and some of them contain unique and unusual biochemical pathways. A number of products from such pathways, especially, the secondary metabolite (SM) pathways are used as important pharmaceuticals, including antibiotics, statins, and immunodepresants. Under different conditions, the individual species can produce more than 100 SM. The strain improvement programs lead to high yielding in target SM and significant reduction of spin-off products. The main tool for the strain improvement of filamentous fungi is random mutagenesis and screening. The majority of industrial overproducing SM strains were developed with the help of such technique over the past 50–70 years; the yield of the target SM increased by 100- to 1000-fold or more. Moreover, most of the strains have reached their technological limit of improvement. A new round of mutagenesis has not increased overproduction. Recently, it was shown that that the addition of exogenous polyamines may increase the production of such improved strains of filamentous fungi. The possible molecular mechanism of this phenomenon and its biotechnological applications are discussed.
{"title":"Random Mutagenesis of Filamentous Fungi Strains for High-Yield Production of Secondary Metabolites: The Role of Polyamines","authors":"A. Zhgun","doi":"10.5772/intechopen.93702","DOIUrl":"https://doi.org/10.5772/intechopen.93702","url":null,"abstract":"A filamentous fungus (also called molds or moldy fungus) is a taxonomically diverse organism from phylum Zygomycota and Ascomycota with filamentous hyphae and has the ability to produce airborne spores or conidia. Currently, more than 70,000 molds are known, and some of them contain unique and unusual biochemical pathways. A number of products from such pathways, especially, the secondary metabolite (SM) pathways are used as important pharmaceuticals, including antibiotics, statins, and immunodepresants. Under different conditions, the individual species can produce more than 100 SM. The strain improvement programs lead to high yielding in target SM and significant reduction of spin-off products. The main tool for the strain improvement of filamentous fungi is random mutagenesis and screening. The majority of industrial overproducing SM strains were developed with the help of such technique over the past 50–70 years; the yield of the target SM increased by 100- to 1000-fold or more. Moreover, most of the strains have reached their technological limit of improvement. A new round of mutagenesis has not increased overproduction. Recently, it was shown that that the addition of exogenous polyamines may increase the production of such improved strains of filamentous fungi. The possible molecular mechanism of this phenomenon and its biotechnological applications are discussed.","PeriodicalId":227085,"journal":{"name":"Genotoxicity and Mutagenicity - Mechanisms and Test Methods","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121835754","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 : 2020-05-05DOI: 10.5772/intechopen.91689
Adel M. Abdel-Hakem, Elshimaa M N Abdelhafez
Mutation is the process leading to heritable changes in DNA caused mainly by internal and external factors. Recently, studies on mutagenic agents have been increased due to increasing in mutation-related disease. The antimutagenic effect is desired to prevent mutation on genes or to inactivate the mutagenic agent. It seems that the interest in antimutagenic substances displaying multiple mechanisms of action will be an important trend in the research and development of new antimutagenic compounds in the near future. Therefore, this chapter displays various possible mechanisms of action for antimutagenic agent and introduces different types of antimutagens, natural and synthetic, that are considered very important.
{"title":"Current Trends and Future Perspectives of Antimutagenic Agents","authors":"Adel M. Abdel-Hakem, Elshimaa M N Abdelhafez","doi":"10.5772/intechopen.91689","DOIUrl":"https://doi.org/10.5772/intechopen.91689","url":null,"abstract":"Mutation is the process leading to heritable changes in DNA caused mainly by internal and external factors. Recently, studies on mutagenic agents have been increased due to increasing in mutation-related disease. The antimutagenic effect is desired to prevent mutation on genes or to inactivate the mutagenic agent. It seems that the interest in antimutagenic substances displaying multiple mechanisms of action will be an important trend in the research and development of new antimutagenic compounds in the near future. Therefore, this chapter displays various possible mechanisms of action for antimutagenic agent and introduces different types of antimutagens, natural and synthetic, that are considered very important.","PeriodicalId":227085,"journal":{"name":"Genotoxicity and Mutagenicity - Mechanisms and Test Methods","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133166887","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 : 2020-05-02DOI: 10.5772/intechopen.92327
J. Panneerselvam, D. Qu, C. Houchen, M. Bronze, P. Chandrakesan
Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed as the DNA damage response (DDR). The DDR is a signaling network that includes cell cycle checkpoints and DNA repair and damage tolerance pathways. Failure of the DDR or associated events causes various diseases, including cancer. DDR is primarily mediated by phosphatidylinositol-3-kinase-like protein kinase (PIKKs) family members ataxia-telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related protein (ATR). However, one of the many unanswered questions regarding these signal-transduction pathways is: how does the cell turn the DDR signals on? There was no conclusive demonstration of the involvement of a specific sensory kinase in DDR signals until our recent research on the DCLK1 role in regulating ATM after genotoxic injury. Currently, various studies are demonstrating the importance of DCLK1 in DNA damage response. Here, we discuss the novel insights into the role of DCLK1 in DNA damage response.
{"title":"DCLK1 and DNA Damage Response","authors":"J. Panneerselvam, D. Qu, C. Houchen, M. Bronze, P. Chandrakesan","doi":"10.5772/intechopen.92327","DOIUrl":"https://doi.org/10.5772/intechopen.92327","url":null,"abstract":"Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed as the DNA damage response (DDR). The DDR is a signaling network that includes cell cycle checkpoints and DNA repair and damage tolerance pathways. Failure of the DDR or associated events causes various diseases, including cancer. DDR is primarily mediated by phosphatidylinositol-3-kinase-like protein kinase (PIKKs) family members ataxia-telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related protein (ATR). However, one of the many unanswered questions regarding these signal-transduction pathways is: how does the cell turn the DDR signals on? There was no conclusive demonstration of the involvement of a specific sensory kinase in DDR signals until our recent research on the DCLK1 role in regulating ATM after genotoxic injury. Currently, various studies are demonstrating the importance of DCLK1 in DNA damage response. Here, we discuss the novel insights into the role of DCLK1 in DNA damage response.","PeriodicalId":227085,"journal":{"name":"Genotoxicity and Mutagenicity - Mechanisms and Test Methods","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126161096","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 : 2020-03-12DOI: 10.5772/INTECHOPEN.91630
I. Gaivão, João Ferreira, L. Sierra
Genotoxicological studies are emerging as fundamental for knowing the hazards to our genome, to our health. Drosophila melanogaster is one of the preferable organisms for toxicological research considering its metabolic similarities (viz. on dietary input, xenobiotic metabolizing system, antioxidant enzymes and DNA repair systems) to mammals. Accordingly, somatic mutation and recombination tests (SMARTs) of D. melanogaster are fast and low-cost in vivo assays that have shown solid results evaluating genotoxicity. The w/w + SMART uses the white (w) gene as a recessive marker to monitor the presence of mutant ommatidia (eye units), indicating the occurrence of point mutations, deletions, mitotic recombination or/and nondisjunction. Additionally, several studies used SMARTs to assess antigenotoxicity, with some using the w/w + SMART. We reviewed the state of the art of the w/w + SMART used for antigenotoxicity analysis, focusing on published results, aiming to contribute to the conception of a reliable protocol in antigenotoxicity. As such, genotoxic agents with known action mechanisms, as streptonigrin (oxidative stress inducer), were used as a genotoxic insult for proving the antigenotoxic effects of natural substances (e.g. seaweeds), demonstrating the presence of antimutagens in their composition. These antigenotoxicity studies are crucial for promoting preventive measures against environmental genotoxics that affect humans daily.
{"title":"The w/w + Somatic Mutation and Recombination Test (SMART) of Drosophila melanogaster for Detecting Antigenotoxic Activity","authors":"I. Gaivão, João Ferreira, L. Sierra","doi":"10.5772/INTECHOPEN.91630","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.91630","url":null,"abstract":"Genotoxicological studies are emerging as fundamental for knowing the hazards to our genome, to our health. Drosophila melanogaster is one of the preferable organisms for toxicological research considering its metabolic similarities (viz. on dietary input, xenobiotic metabolizing system, antioxidant enzymes and DNA repair systems) to mammals. Accordingly, somatic mutation and recombination tests (SMARTs) of D. melanogaster are fast and low-cost in vivo assays that have shown solid results evaluating genotoxicity. The w/w + SMART uses the white (w) gene as a recessive marker to monitor the presence of mutant ommatidia (eye units), indicating the occurrence of point mutations, deletions, mitotic recombination or/and nondisjunction. Additionally, several studies used SMARTs to assess antigenotoxicity, with some using the w/w + SMART. We reviewed the state of the art of the w/w + SMART used for antigenotoxicity analysis, focusing on published results, aiming to contribute to the conception of a reliable protocol in antigenotoxicity. As such, genotoxic agents with known action mechanisms, as streptonigrin (oxidative stress inducer), were used as a genotoxic insult for proving the antigenotoxic effects of natural substances (e.g. seaweeds), demonstrating the presence of antimutagens in their composition. These antigenotoxicity studies are crucial for promoting preventive measures against environmental genotoxics that affect humans daily.","PeriodicalId":227085,"journal":{"name":"Genotoxicity and Mutagenicity - Mechanisms and Test Methods","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127846344","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 : 2020-01-10DOI: 10.5772/intechopen.90861
M. Rojas-Lemus, P. Bizarro-Nevares, N. López-Valdez, A. González-Villalva, Gabriela Guerrero-Palomo, Cervantes-Valencia María Eugenia, Otto Tavera-Cabrera, Norma Rivera-Fernández, Brenda Casarrubias-Tabarez, M. Ustarroz-Cano, Armando Rodríguez-Zepeda, F. Pasos-Nájera, T. F. Goes
Air pollution is a worldwide health problem, and metals are one of the various air pollutants to which living creatures are exposed. The pollution by metals such as: lead, cadmium, manganese, and vanadium have a common mechanism of action: the production of oxidative stress in the cell. Oxidative stress favors the production of free radicals, which damage biomolecules such as: DNA, proteins, lipids, and carbohydrates; these free radicals produce changes that are observed in different organs and systems. Vanadium is a transition element delivered into the atmosphere by the combustion of fossil fuels as oxides and adhered to the PM enters into the respiratory system, then crosses the alveolar wall and enters into the systemic circulation. In this chapter, we will review the oxidative stress induced by vanadium—as a common mechanism of metal pollutants—; in addition, we will review the protective effect of the antioxidants (carnosine and ascorbate).
{"title":"Oxidative Stress and Vanadium","authors":"M. Rojas-Lemus, P. Bizarro-Nevares, N. López-Valdez, A. González-Villalva, Gabriela Guerrero-Palomo, Cervantes-Valencia María Eugenia, Otto Tavera-Cabrera, Norma Rivera-Fernández, Brenda Casarrubias-Tabarez, M. Ustarroz-Cano, Armando Rodríguez-Zepeda, F. Pasos-Nájera, T. F. Goes","doi":"10.5772/intechopen.90861","DOIUrl":"https://doi.org/10.5772/intechopen.90861","url":null,"abstract":"Air pollution is a worldwide health problem, and metals are one of the various air pollutants to which living creatures are exposed. The pollution by metals such as: lead, cadmium, manganese, and vanadium have a common mechanism of action: the production of oxidative stress in the cell. Oxidative stress favors the production of free radicals, which damage biomolecules such as: DNA, proteins, lipids, and carbohydrates; these free radicals produce changes that are observed in different organs and systems. Vanadium is a transition element delivered into the atmosphere by the combustion of fossil fuels as oxides and adhered to the PM enters into the respiratory system, then crosses the alveolar wall and enters into the systemic circulation. In this chapter, we will review the oxidative stress induced by vanadium—as a common mechanism of metal pollutants—; in addition, we will review the protective effect of the antioxidants (carnosine and ascorbate).","PeriodicalId":227085,"journal":{"name":"Genotoxicity and Mutagenicity - Mechanisms and Test Methods","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124698661","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 : 2019-12-13DOI: 10.5772/intechopen.89563
V. Mykhailenko, V. Kyrychenko, A. Bragin, Dmitry Chuiko
A majority of sunflower lines and hybrids were based on starting material obtained by traditional methods; so the issues of developing new trends in extending the genetic diversity of this crop require constant attention of scientists. At present, induced mutagenesis along with hybridization has become a leading method for generating new forms of crops. Their success depends largely on availability and assortment of starting material. Induction of mutations is a way to create it. The main value of induced mutagenesis for breeding is determined by opportunities to solve problems that are impossible or difficult to solve by traditional methods. The choice of an effective concentration (dose) of a mutagen is very important, since the frequency and range of mutations depend not only on the mutagen itself but also on its dose and exposure. In addition, it is relevant to search for new mutagens with reduced harmful effects at the same level of mutability. Cytological analysis of chromosomal aberrations is an important method of evaluation and identification of mutagenic effects. In this section, studies into chemical and physical mutagenesis in breeding, exemplified by new modern homozygous self-pollinated sunflower lines, are summarized; methodical recommendations on the use of induced mutagenesis in sunflower breeding are presented; and methods of generation, investigation, and further use of mutations are rationalized.
{"title":"Generation, Evaluation, and Prospects of Further Use of Mutations Based on New Homozygous Self-Pollinated Sunflower Lines","authors":"V. Mykhailenko, V. Kyrychenko, A. Bragin, Dmitry Chuiko","doi":"10.5772/intechopen.89563","DOIUrl":"https://doi.org/10.5772/intechopen.89563","url":null,"abstract":"A majority of sunflower lines and hybrids were based on starting material obtained by traditional methods; so the issues of developing new trends in extending the genetic diversity of this crop require constant attention of scientists. At present, induced mutagenesis along with hybridization has become a leading method for generating new forms of crops. Their success depends largely on availability and assortment of starting material. Induction of mutations is a way to create it. The main value of induced mutagenesis for breeding is determined by opportunities to solve problems that are impossible or difficult to solve by traditional methods. The choice of an effective concentration (dose) of a mutagen is very important, since the frequency and range of mutations depend not only on the mutagen itself but also on its dose and exposure. In addition, it is relevant to search for new mutagens with reduced harmful effects at the same level of mutability. Cytological analysis of chromosomal aberrations is an important method of evaluation and identification of mutagenic effects. In this section, studies into chemical and physical mutagenesis in breeding, exemplified by new modern homozygous self-pollinated sunflower lines, are summarized; methodical recommendations on the use of induced mutagenesis in sunflower breeding are presented; and methods of generation, investigation, and further use of mutations are rationalized.","PeriodicalId":227085,"journal":{"name":"Genotoxicity and Mutagenicity - Mechanisms and Test Methods","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127865517","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 : 2019-12-12DOI: 10.5772/intechopen.90356
M. Fasullo
This review discusses using yeast as a model organism for studying the biological effects of P450-mediated metabolism of xenobiotics. We discuss the challenges of testing the safety of thousands of chemicals currently introduced into the market place, the limitations of the animal systems, the advantages of model organisms, and the humanization of the yeast cells by expressing human cytochrome P450 (CYP) genes. We discuss strategies in utilizing multiple genetic endpoints in screening chemicals and yeast strains that facilitate phenotyping CYP polymorphisms. In particular, we discuss yeast mutants that facilitate xenobiotic import and retention and particular DNA repair mutants that can facilitate in measuring genotoxic endpoints and elucidating genotoxic mechanisms. New directions in toxicogenetics suggest that particular DNA damaging agents may interact with chromatin and perturb gene silencing, which may also generate genetic instabilities. By introducing human CYP genes into yeast strains, new strategies can be explored for high-throughput testing of xenobiotics and identifying potent DNA damaging agents.
{"title":"Genotoxic Assays for Measuring P450 Activation of Chemical Mutagens","authors":"M. Fasullo","doi":"10.5772/intechopen.90356","DOIUrl":"https://doi.org/10.5772/intechopen.90356","url":null,"abstract":"This review discusses using yeast as a model organism for studying the biological effects of P450-mediated metabolism of xenobiotics. We discuss the challenges of testing the safety of thousands of chemicals currently introduced into the market place, the limitations of the animal systems, the advantages of model organisms, and the humanization of the yeast cells by expressing human cytochrome P450 (CYP) genes. We discuss strategies in utilizing multiple genetic endpoints in screening chemicals and yeast strains that facilitate phenotyping CYP polymorphisms. In particular, we discuss yeast mutants that facilitate xenobiotic import and retention and particular DNA repair mutants that can facilitate in measuring genotoxic endpoints and elucidating genotoxic mechanisms. New directions in toxicogenetics suggest that particular DNA damaging agents may interact with chromatin and perturb gene silencing, which may also generate genetic instabilities. By introducing human CYP genes into yeast strains, new strategies can be explored for high-throughput testing of xenobiotics and identifying potent DNA damaging agents.","PeriodicalId":227085,"journal":{"name":"Genotoxicity and Mutagenicity - Mechanisms and Test Methods","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116330964","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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