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Anais Da Academia Brasileira de Ciencias Dec 2007The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the... (Review)
Review
The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair--i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.
Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Humans; Neoplasms; Risk Factors
PubMed: 18066431
DOI: 10.1590/s0001-37652007000400004 -
Comptes Rendus Biologies Sep 2023Replication stress is an alteration in the progression of replication forks caused by a variety of events of endogenous or exogenous origin. In precancerous lesions,... (Review)
Review
Replication stress is an alteration in the progression of replication forks caused by a variety of events of endogenous or exogenous origin. In precancerous lesions, this stress is exacerbated by the deregulation of oncogenic pathways, which notably disrupts the coordination between replication and transcription, and leads to genetic instability and cancer development. It is now well established that transcription can interfere with genome replication in different ways, such as head-on collisions between polymerases, accumulation of positive DNA supercoils or formation of R-loops. These structures form during transcription when nascent RNA reanneals with DNA behind the RNA polymerase, forming a stable DNA:RNA hybrid. In this review, we discuss how these different cotranscriptional processes disrupt the progression of replication forks and how they contribute to genetic instability in cancer cells.
Topics: Transcription, Genetic; R-Loop Structures; DNA Replication; DNA; Oncogenes; RNA; Neoplasms
PubMed: 37779381
DOI: 10.5802/crbiol.123 -
Nature Materials Jul 2020Defining the interplay between the genetic events and microenvironmental contexts necessary to initiate tumorigenesis in normal cells is a central endeavour in cancer...
Defining the interplay between the genetic events and microenvironmental contexts necessary to initiate tumorigenesis in normal cells is a central endeavour in cancer biology. We found that receptor tyrosine kinase (RTK)-Ras oncogenes reprogram normal, freshly explanted primary mouse and human cells into tumour precursors, in a process requiring increased force transmission between oncogene-expressing cells and their surrounding extracellular matrix. Microenvironments approximating the normal softness of healthy tissues, or blunting cellular mechanotransduction, prevent oncogene-mediated cell reprogramming and tumour emergence. However, RTK-Ras oncogenes empower a disproportional cellular response to the mechanical properties of the cell's environment, such that when cells experience even subtle supra-physiological extracellular-matrix rigidity they are converted into tumour-initiating cells. These regulations rely on YAP/TAZ mechanotransduction, and YAP/TAZ target genes account for a large fraction of the transcriptional responses downstream of oncogenic signalling. This work lays the groundwork for exploiting oncogenic mechanosignalling as a vulnerability at the onset of tumorigenesis, including tumour prevention strategies.
Topics: Animals; Biomechanical Phenomena; Cell Line, Tumor; Cellular Reprogramming; Extracellular Matrix; Female; Gene Expression Regulation; Humans; Mammary Glands, Human; Mice; Mice, Inbred Strains; Mice, Knockout; Microscopy; Oncogenes; Pancreas; Sequence Analysis, RNA
PubMed: 32066931
DOI: 10.1038/s41563-020-0615-x -
IARC Monographs on the Evaluation of... 2000
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Cricetinae; Disease Models, Animal; Environmental Exposure; Epoxy Compounds; Female; Humans; Male; Maximum Allowable Concentration; Mice; Neoplasms, Experimental; Propanols; Rats
PubMed: 11100412
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Chromosome Aberrations; Dioxanes; Humans; Mutagenicity Tests; Mutagens; Neoplasms; Neoplasms, Experimental; Salmonella typhimurium
PubMed: 10476463
DOI: No ID Found -
IARC Monographs on the Evaluation of... 2000
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Disease Models, Animal; Environmental Exposure; Ethanolamines; Female; Humans; Industrial Oils; Male; Maximum Allowable Concentration; Mice; Neoplasms; Rats; Reproduction
PubMed: 11100408
DOI: No ID Found -
IARC Monographs on the Evaluation of... 2000
Review
Topics: Animals; Carcinogens; Disease Models, Animal; Environmental Exposure; Ethanolamines; Female; Humans; Industrial Oils; Male; Maximum Allowable Concentration; Mice; Neoplasms; Rats; Reproduction
PubMed: 11100407
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Insecticides; Mutagenicity Tests; Mutagens; Neoplasms; Neoplasms, Experimental; Propane
PubMed: 10476458
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Acetaldehyde; Animals; Carcinogenicity Tests; Carcinogens; Humans; Mutagenicity Tests; Mutagens; Neoplasms; Neoplasms, Experimental; Occupational Exposure
PubMed: 10476449
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Review
Topics: 2-Propanol; Animals; Carcinogenicity Tests; Carcinogens; Humans; Neoplasms; Neoplasms, Experimental; Occupational Exposure
PubMed: 10476373
DOI: No ID Found