Human Genetics, Leiden. Examination There will be no examination. Participants will be required to actively take part in discussions following the lectures and during the practical work and will give a short presentation about the outcome of the Ames test. In this module, we will focus on i the different types of damage that can be formed in the DNA of our cells either spontaneously or because of exposure to DNA damaging agents in the environment, ii the cellular defense mechanisms that preserve genetic integrity and iii the biological consequences of non-repaired DNA damage in particular the induction of mutations in relation to the development of cancer Aim of the course The aim of the course is to familiarize participants with the mechanisms by which DNA damage causes genetic alterations and cancer and the cellular processes which protect human beings from the deleterious effects of DNA damaging agents.
The participant knows the potency of short term test in evaluation studies on mutagenicity and carcinogenicity. The participant understands the difference between DNA damage and DNA mutation and the differential impact of hereditary versus somatic mutations for enhancing cancer risk.
The participant can deduce and explain the consequences of defects in various cellular processes that aim to protect the individual against cancer. Human Genetics, Leiden Examination There will be no examination. It was found that the removal of DNA photolesions was much less efficient in rad9 mutant cells than normal cells, providing evidence that RAD9 is involved in DNA repair. It is in this way that RAD9 is able to exert its effects. Although the function of RAD9 has primarily been studied in the budding yeast Saccharomyces cerevisiae, many of the cell cycle control mechanisms are similar between species.
From Wikipedia, the free encyclopedia. Main article: DNA repair. Springer, Cham. Cancer and aging as consequences of un-repaired DNA damage. New England Journal of Medicine. PLOS Genetics. Khan Academy. Retrieved Molecular Cell. In Chen C ed. Rijeka, Croatia: InTech.
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Van Nostrand Reinhold, New York. Pages — Trends in Biochemical Sciences. Journal of Nucleic Acids. Toxicological Sciences. Cold Spring Harbor Perspectives in Biology. Oncology Williston Park, N. Trends in Cell Biology. Annual Review of Biochemistry. FEBS Letters. Experimental Oncology. Annual Review of Pathology: Mechanisms of Disease. Journal of Clinical Oncology.
Mutagenesis and Carcinogenesis
Isrn Oncology. Correlation with etiology, histology and cell proliferation". Gut Microbes. Alimentary Pharmacology and Therapeutics. European Journal of Clinical Nutrition. Clinical and Experimental Gastroenterology. Archives of Toxicology. Current Colorectal Cancer Reports. Toxicology Letters. Current Genomics. Molecular Biology of the Cell. Journal of Cell Science. The Journal of Cell Biology. Cell Reports. Journal of Biological Chemistry. Nature Cell Biology.
Journal of the American Chemical Society. Cellular and Molecular Life Sciences. DNA Repair. Nature Neuroscience. Cellular Signalling. Biochemistry and Cell Biology. Journal of Neuroscience. DNA Repair Amst 9 12 — DNA Repair Amst. Molecular and Cellular Biology. Rao and P. The experiment has a previously established duration and the animals that survive are sacrificed at the end of the experiment van Leeuwen and Zonneveld , Pitot , Payne and Kemp Animals are examined post-mortem in order to evaluate the incidence of neoplasic development and other pathological changes.
Statistical analysis is used to evaluate if the neoplasic incidence is significantly different from the control group Ito et al. Carcinogenic assays on rodents identify potential carcinogens for humans. Achieving a positive result on a conventional essay indicates that there exists only a potential danger. Its meaning for human health will depend on other factors, some of which require additional studies Maronpot and Boorman The extrapolation of results obtained via experimental work with rodents is contested by the following arguments Gaylor and Chen , Huff , Tennant et al.
Molecular biology has provided new models with which to study carcinogenesis with the development of transgenic and knockout rodents. Some models have mutations in the ras proto-oncogenes and in the psuppressor gene Sills et al. Animal models deficient in p53 protein and ras genes are more sensitive to the identification of genotoxic carcinogens Sills et al. According to Pritchard et al. Although these models are promising, they also have limitations because they can exhibit metabolic alterations, which are not consistently relevant to carcinogenesis.
In addition, mutated genes can influence the nature of neoplasia that is developed, increasing the difficulty of measuring the response in humans Pritchard et al. It is necessary to pay attention to the analysis of the results, because there is evidence which indicates that carcinogens can act through specific mechanisms.
The premise that those carcinogenic compounds experimentally tested are harmful for man is not always valid Swenberg et al. The results obtained using rodents act as back-up against any false negatives obtained through in vitro researches and can be used to prevent, or reduce, human exposure to a suspected carcinogen Payne and Kemp Epidemiological studies provide a great deal of information about exposure to those chemicals present in food, the environment and at work, but are limited as far as the identification of etiological factors are concerned, especially in cases where neoplasic development results from the interaction of multiple agents Garner , Tennant , Weinstein Epidemiological studies are retrospective and unless a large number of individuals are studied their sensitivity is reduced Weinstein ,Tennant Epidemiological techniques have been useful for identifying exposure to high carcinogenic concentrations.
Yet, it is difficult to understand the individual contribution of a certain chemical within a complex situation like environmental contamination. Carrying out epidemiological studies of a scientific nature is difficult for several reasons Farmer , Tennant :. The carcinogenic influence of a substance can be determined using computer programmes that thoroughly simulate man's physiological and metabolic procedures and relate them to the molecular configuration of the substance being studied Loew et al.
These chemical properties are related to the molecular structure of chemical, physical, and toxicological properties Barratt and Rodford , Feng et al.
Statistical learning methods have recently been explored as a new approach for genotoxicity prediction without any restrictions on the features of structures or types of molecules. Instead of focusing on specific structural features or a particular group of related molecules, these methods classify molecules into genotoxic positive or non-genotoxic agents based on their general structural and physicochemical properties, regardless of their structural and chemical types Li et al. Other available tests concern the use of protozoa cultures and the chorioallantoic membrane.
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The ciliated protozoan Tetrahymena pyriformis may be used in bioassays to evaluate the cytotoxic impact of many chemical compounds Bonnet et al. The chicken chorioallantoic membrane assay is used to study angiogenesis during tumour growth Tufan and Satiroglu-Tufan In summary, our objectives for this article were to review the current information available on chemical carcinogenesis. Chemical carcinogenesis is a multistage and multicausal process in which normal cells become first initiated, then malignant and invasive. Each of these stages is exceedingly complex in itself.
The acquisition of the capacity to survive and grow independently from other cells represents a crucial event in the mechanism of cancer development. Most of the morphological, biochemical and genetic changes currently observed should be considered as the expression of the adaptation of neoplasic cells to survive in a familiar but hostile environment.
The prediction of chemical carcinogenicity is of great importance to human risk assessment. Inorganic arsenite-induced malignant transformation of human prostate epithelial cells. J Natl Cancer Inst Carcinogen-DNA adducts as tools in risk assessment. Adv Exp Med Biol Cancer Prediction of Rodent Carcinogenicity for 30 Chemicals.
Environ Health Perspect S: Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis. BMC Cancer 9: The uses of carcinogen-DNA adduct measurement in establishing mechanisms of mutagenesis and in chemoprevention. Mutat Res Carcinogenesis in mouse and human cells: parallels and paradoxes. Carcinogenesis The computational prediction of toxicity.
Opin Chem Biol 5: Mechanisms of multistep carcinogenesis and carcinogen risk assessment. Environ Health Perspect Molecular mechanisms of carcinogenesis in humans and rodents. Mol Carcinog 7: Cellular and molecular mechanisms of multistep carcinogenesis: relevance to carcinogen risk assessment. The role of individual susceptibility in cancer burden related to environmental exposure.
The role of croton oil applications, associated with a single painting of a carcinogen, in tumor induction of the mouse's skin. Br J Cancer 1: The molecular biology of cancer. Mol Aspects Med Molecular theory of cancer. Cancer Biol Ther 4: Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective. Toxicol Lett Estimated risk in malignancy: the emerging field of molecular epidemiology. Clin Adv Hematol Oncol 2: Cytotoxic assessment of three therapeutic agents, cyclosporine-A, cisplatin and doxorubicin, with the ciliated protozoan Tetrahymena pyriformis.
Res Microbiol A comprehensive approach for integration of toxicity and cancer risk assessments. Regul Toxicol Pharmacol Chemically induced cell proliferation in carcinogenesis. Long-term mutagenicity studies with chloroform and dimethylnitrosamine in female lacI transgenic B6C3F1 mice.
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Drug Metab Rev Genetic errors, cell proliferation, and carcinogenesis. Cancer Res Rodent bladder tumors do not always predict for humans. Cancer Lett Ideas in pathology. Pivotal role of increased cell proliferation in human carcinogenesis. Mod Pathol 4: Cancer enhancement by cell proliferation.
Prog Clin Biol Res Pharmacokinetics, biochemical mechanism and mutation accumulation: a comprehensive model of chemical carcinogenesis. J Environ Monit 5: Carcinogenic effects of hyperthermia.http://www.nurmektebiirfani.com/includes
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