About this Research Topic
Background:
In genetics, genotoxicity refers to the harmful effect of various substances on genetic information. Genotoxic agents, such as chemical and biological agents and radiation, can act in different ways. They can directly cause gene mutations, interfere with DNA and chromosomal replication or repair mechanisms, or indirectly induce oxidative stress which lead to DNA damage, and modify epigenetic regulation of DNA repair genes. The consequences of genotoxicity can range from minor DNA lesions that can be repaired by the cell's natural repair mechanisms to severe damage that affect genome integrity and lead to serious health consequences.
Evaluation of genotoxicity is critical in various fields, including toxicology, pharmaceutical development, environmental health, and regulatory sciences. Understanding the genotoxic potential of substances is vital for assessing their safety, guiding the development of new drugs and chemicals, and setting regulatory guidelines for their use.
Goal:
Numerous testing approaches and assays have been developed to assess genotoxicity, including in vitro and in vivo techniques, as well as bioinformatic approaches. In recent years, high-throughput genotoxicity assessments which combined both in vitro and in vivo assays have been employed widely for genotoxicity evaluation. The advent of next generation sequencing (NGS) instruments provides us with powerful tools to characterize genomic toxicology, at genome-wide scale with unprecedented resolution. However, no single test is capable by itself to detect all genotoxic aspects. For example, the Ames’ test, based on bacteria strains, cannot fully represent a mammal’s genetic scenario and complicated DNA repair systems. Different experiment factors and conditions imposed huge variability to comet assay outcomes. Error correction becomes a necessity for NGS to improve accuracy. Sequencing both strands of the DNA allows validation that a mutation is real and not a sequencing artifact. The goal of the research topic is to motivate novel testing methods with higher sensitivity and specificity to detect different types of genotoxicity, which will ultimately translate to clinical use.
Scope and Information for Authors:
This research topic aims to explore new assay technologies and applications in the field of genotoxicity testing. Our scopes of work include but are not limited to the following themes:
1) Discussion and modification of existing short-term test assays, including Ames test, Micronuclei test, Comet Assay, Thymidine kinase Assay, and ROSGlo assay.
2) New technologies, especially RT-qPCR based multiple biomarker assays and NGS based tests, such as Error-corrected NGS, Single Cell Sequencing, and Direct Single-Molecule Sequencing. These technologies will enable us to detect genome structural variations in low-abundant events.
3) Quantification and pharmacokinetics and pharmacodynamics (PK-PD) modelling in this field.
4) Typically, different genotoxicity assays differ by their detection targets and mechanisms. They each identify one or limited types of genetic material damage, but are generally not comprehensive. Any exploration and discussion to integrate different assays into biological pathways and health risk scores will allow further translation into clinical use.
In genetics, genotoxicity refers to the harmful effect of various substances on genetic information. Genotoxic agents, such as chemical and biological agents and radiation, can act in different ways. They can directly cause gene mutations, interfere with DNA and chromosomal replication or repair mechanisms, or indirectly induce oxidative stress which lead to DNA damage, and modify epigenetic regulation of DNA repair genes. The consequences of genotoxicity can range from minor DNA lesions that can be repaired by the cell's natural repair mechanisms to severe damage that affect genome integrity and lead to serious health consequences.
Evaluation of genotoxicity is critical in various fields, including toxicology, pharmaceutical development, environmental health, and regulatory sciences. Understanding the genotoxic potential of substances is vital for assessing their safety, guiding the development of new drugs and chemicals, and setting regulatory guidelines for their use.
Goal:
Numerous testing approaches and assays have been developed to assess genotoxicity, including in vitro and in vivo techniques, as well as bioinformatic approaches. In recent years, high-throughput genotoxicity assessments which combined both in vitro and in vivo assays have been employed widely for genotoxicity evaluation. The advent of next generation sequencing (NGS) instruments provides us with powerful tools to characterize genomic toxicology, at genome-wide scale with unprecedented resolution. However, no single test is capable by itself to detect all genotoxic aspects. For example, the Ames’ test, based on bacteria strains, cannot fully represent a mammal’s genetic scenario and complicated DNA repair systems. Different experiment factors and conditions imposed huge variability to comet assay outcomes. Error correction becomes a necessity for NGS to improve accuracy. Sequencing both strands of the DNA allows validation that a mutation is real and not a sequencing artifact. The goal of the research topic is to motivate novel testing methods with higher sensitivity and specificity to detect different types of genotoxicity, which will ultimately translate to clinical use.
Scope and Information for Authors:
This research topic aims to explore new assay technologies and applications in the field of genotoxicity testing. Our scopes of work include but are not limited to the following themes:
1) Discussion and modification of existing short-term test assays, including Ames test, Micronuclei test, Comet Assay, Thymidine kinase Assay, and ROSGlo assay.
2) New technologies, especially RT-qPCR based multiple biomarker assays and NGS based tests, such as Error-corrected NGS, Single Cell Sequencing, and Direct Single-Molecule Sequencing. These technologies will enable us to detect genome structural variations in low-abundant events.
3) Quantification and pharmacokinetics and pharmacodynamics (PK-PD) modelling in this field.
4) Typically, different genotoxicity assays differ by their detection targets and mechanisms. They each identify one or limited types of genetic material damage, but are generally not comprehensive. Any exploration and discussion to integrate different assays into biological pathways and health risk scores will allow further translation into clinical use.
Keywords: Genotoxicity; Toxicogenomics; Mutagenicity; Cytogenetics; Methylation; Oxidative Stress; Micronuclei; Comet; Sequencing.
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