Radiation Carcinogenesis and DNA Alterations

This volume is based on the proceedings of an Advanced Study Institute (ASI) sponsored by the North Atlantic Treaty Organization (NATO) held October 1984 in Corfu, Greece.

Author: Frederic J. Burns

Publisher: Springer Science & Business Media

ISBN: 9781468452693

Category: Medical

Page: 618

View: 190

Download →

This volume is based on the proceedings of an Advanced Study Institute (ASI) sponsored by the North Atlantic Treaty Organization (NATO) held October 1984 in Corfu, Greece. The meeting received finan cial support from the United States Department of Energy and the United States National Cancer Institute. A plethora of recent developments in the molecular biology of DNA are leading to new ideas concerning how DNA alterations might be involved in the mechanism of radiation carcinogenesis. Evidence is accumulating that genetic sequences, known as oncogenes, are involved in the translation of DNA molecular alterations into phenotypic changes associated with malignant cells. For example, a chromosome break often occurs at or near the loca tion of a specific oncogene in Burkitt's lymphoma. Such breaks could represent initial lesions in a translocation process that activates the oncogene by inserting it at a new location, eg., near an active pro moter. Since breakage of the DNA is one of the principal ways that ion izing radiation affects mammalian cells, these new molecular ideas sug gest ways that radiation-induced DNA breaks might be involved as initial events in carcinogenesis. While the possible involvement of oncogenes in radiation carcino genesis is an exciting new development, a direct sequential connection between early molecular changes in DNA and later tumor development has yet to be established. Accordingly, there is a tremendous need for experimental studies of how DNA alterations might convert normal cells to cancer cells.
Posted in:

Aging Carcinogenesis and Radiation Biology

The covalent attachment to deoxyribonucleic acid in vivo of a large number of different types of chemical compounds (both normal cellular constituents such as proteins and amino acids, and also exogenous compounds such as drugs, carcinogens ...

Author: Kendric Smith

Publisher: Springer Science & Business Media

ISBN: 9781475716627

Category: Medical

Page: 561

View: 400

Download →

The covalent attachment to deoxyribonucleic acid in vivo of a large number of different types of chemical compounds (both normal cellular constituents such as proteins and amino acids, and also exogenous compounds such as drugs, carcinogens, etc. ) have been shown to exert profound effects upon cells. Four research activi ties, formerly considered to be totally independent, relate to this problem of nucleic acid adducts--(1) normal covalent attachment of DNA to membranes, protein linkers in chromosomes, etc. ; (2) the roles of radiation and chemical enhancement of DNA adduct formation in cell killing and mutagenesis. (A related field is the use of known cross-linking reactions to gain information on structural associations in macromolecular complexes. ); (3) the relevance of DNA adducts to chemical and radiation carcinogenesis; (4) the rele vance of DNA adducts to the cross-linking theory of cellular aging. (1) There are numerous examples of normal linkages between DNA and protein, e. g. , DNA-membrane attachment sites, protein linkers in chromosomes, amino acids covalently linked to DNA as a function of growth conditions, and gene regulation by non-covalently bound proteins. A summary of data on natural adducts to DNA thus serves to introduce the subject of the radiation and chemical enhancement of DNA adduct formation. (2) In the past, radiation biology has been concerned mainly with trying to understand the radiation chemistry of purified DNA, and the biological effects and repair of these radiation-induced alterations when produced in cellular DNA.
Posted in:

Alterations of Epigenetics and MicroRNAs in Cancer and Cancer Stem Cell

MiRNAs are small non-coding RNAs that regulate expression of various target genes. Specific miRNAs are aberrantly expressed and play roles as tumor suppressors or oncogenes during carcinogenesis.

Author: Yoshimasa Saito

Publisher: Frontiers E-books

ISBN: 9782889193455

Category: Biology (General)

Page: 79

View: 876

Download →

Studies have shown that alterations of epigenetics and microRNAs (miRNAs) play critical roles in the initiation and progression of human cancer. Epigenetic silencing of tumor suppressor genes in cancer cells is generally mediated by DNA hypermethylation of CpG island promoter and histone modification such as methylation of histone H3 lysine 9 (H3K9) and tri-methylation of H3K27. MiRNAs are small non-coding RNAs that regulate expression of various target genes. Specific miRNAs are aberrantly expressed and play roles as tumor suppressors or oncogenes during carcinogenesis. Important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in activation of target oncogenes in human malignancies. Stem cells have the ability to perpetuate themselves through self-renewal and to generate mature cells of various tissues through differentiation. Accumulating evidence suggests that a subpopulation of cancer cells with distinct stem-like properties is responsible for tumor initiation, invasive growth, and metastasis formation, which is defined as cancer stem cells. Cancer stem cells are considered to be resistant to conventional chemotherapy and radiation therapy, suggesting that these cells are important targets of cancer therapy. DNA methylation, histone modification and miRNAs may be deeply involved in stem-like properties in cancer cells. Restoring the expression of tumor suppressor genes and miRNAs by chromatin modifying drugs may be a promising therapeutic approach for cancer stem cells. In this Research Topic, we discuss about alterations of epigenetics and miRNAs in cancer and cancer stem cell and understand the molecular mechanism underlying the formation of cancer stem cell, which may provide a novel insight for treatment of refractory cancer.
Posted in:

Molecular Determinants of Radiation Response

Given the importance of therapies that induce DNA injury in the management of human disease, this book is timely and relevant for basic and translational researchers, as well as clinicians alike.

Author: Theodore L. DeWeese

Publisher: Springer Science & Business Media

ISBN: 144198044X

Category: Medical

Page: 276

View: 220

Download →

Molecular Determinants of Radiation Response includes chapters by expert authors who detail the present understanding of key DNA damage response pathways and proteins. The chapters include comprehensive discussions on where and how specific alterations in function of these pathways and proteins result in substantive modifications of cellular response to DNA injury. Given the importance of therapies that induce DNA injury in the management of human disease, this book is timely and relevant for basic and translational researchers, as well as clinicians alike.
Posted in:

Chromosomal Alterations

The book helps the reader to better understand cytogenetics and the intricacies of the methodology. The different methods of fluorescence in situ hybridization are discussed and the results achieved are presented.

Author: Günter Obe

Publisher: Springer Science & Business Media

ISBN: 9783540714149

Category: Science

Page: 515

View: 208

Download →

The book helps the reader to better understand cytogenetics and the intricacies of the methodology. The different methods of fluorescence in situ hybridization are discussed and the results achieved are presented. The book provides a comprehensive review of basic and applied aspects of cytogenetics and thus is of intense interest to all those interested in chromosomes and their alterations by different types of mutagens, including chemical mutagens and ionizing and nonionizing radiation, with special reference to electromagnetic fields.
Posted in:

The Role of Epigenetics in the Rat Mammary Gland

Epigenetics plays an important role in carcinogenesis with heritable changes in DNA methylation and histone modifications intricately linked to the initiation, promotion, and progression of cancer.

Author: Kristy Kutanzi

Publisher:

ISBN: OCLC:1032943946

Category:

Page:

View: 383

Download →

Posted in:

Cell Transformation Systems Relevant to Radiation Induced Cancer in Man Proceedings of a Workshop Jointly Organised by the Nuclear Energy Board of Ireland the United States Department of Energy and the Commission of the European Communities Held in Du

This book will be of interest to molecular biologists, medical physicists and cancer specialists who require a comprehensive account of the latest work on cell transformation and radiation-induced cancer.

Author: Kenneth Helme Chadwick

Publisher: CRC Press

ISBN: UCAL:B4513968

Category: Medical

Page: 414

View: 867

Download →

The transformation of mammalian cells in vitro provides quantitative and qualitative information on the processes by which physical and chemical agents induce malignancy. Recently, there has been considerable progress on the developmnent of new cell transformation systems and the role of oncogenes in cell transformation. An International Workshop held during April 1989 in Dublin encouraged collaborative interactions between the scientists working in this field and provided a forum for critical review of current research results. Cell Transformation and Radiation-induced Cancer is a record of the papers presented at the Workshop. It includes work which focuses on the potential of emerging human cell transformation systems and their relevance to radiation carcinogenesis, and on the role and interplay of oncogenes, retroviruses and radiation in cell transformation. Particular emphasis is placed on the influence of such variables as radiation quality, dose and dose rate, promoters and suppressors and cell types on in vitro cell transformation. Also considered are the implications of the results from cell transformation studies for radiation-induced cancer in man and for radiological protection. This book will be of interest to molecular biologists, medical physicists and cancer specialists who require a comprehensive account of the latest work on cell transformation and radiation-induced cancer.
Posted in:

The Significance of the Bystander Effect

We argue that integrating short- and long-term models is needed. As an example of this novel approach, we integrated a stochastic short-term initiation/inactivation/repopulation model with a deterministic two-stage long-term model.

Author:

Publisher:

ISBN: OCLC:893413591

Category:

Page:

View: 589

Download →

Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assumed the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions were implemented by a mathematical formalism and computational algorithms. The model adequately described data on bystander responses in the 3D system using a small number of adjustable parameters. Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long-term models is needed. As an example of this novel approach, we integrated a stochastic short-term initiation/inactivation/repopulation model with a deterministic two-stage long-term model. Within this new formalism, the following assumptions are implemented: radiation initiates, promotes, or kills pre-malignant cells; a pre-malignant cell generates a clone, which, if it survives, quickly reaches a size limitation; the clone subsequently grows more slowly and can eventually generate a malignant cell; the carcinogenic potential of pre-malignant cells decreases with age. The effectiveness of high-LET radiation per unit dose increases as dose rate decreases. This "inverse dose rate effect" is seen in radon-induced lung carcinogenesis. We suggest a biologically-motivated mechanism based on radiation-induced direct and bystander-effect-related risks: During radon exposure, only a fraction of cells are traversed by alpha particles. These irradiated cells have an increased probability of being initiated into a pre-malignant state. They release signals, which convert some nearby unirradiated cells to an activated state. When already pre-malignant cells are activated, their proliferation (promotion) rate increases. If a radiation dose is sufficient to activate most susceptible cells, protracting the exposure does not substantially decrease the number of activated cells, but prolongs the activated state during which pre-malignant cell proliferation is accelerated. This mechanism is implemented in a low-dose-rate extension of our carcinogenesis model, which integrates both short- and long-term modeling approaches, and was applied to radiotherapy-induced second cancer risk estimation. Model predictions adequately describe the data on radon-induced lung carcinogenesis in humans and rats, using few adjustable parameters. Conclusions about the relative importance of promotion vs. initiation for radon carcinogenesis are similar to those reported with the two-stage clonal expansion model, but a mechanistic explanation for promotion is provided.
Posted in:

The Oncogenic Action of Ionizing Radiation on Rat Skin

The return of these cells to S-phase a second time was detected by a second label ([sup 3]H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined.

Author:

Publisher:

ISBN: OCLC:727304406

Category:

Page: 62

View: 900

Download →

The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/[mu]), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of [sup 14]C-thymidine. The return of these cells to S-phase a second time was detected by a second label ([sup 3]H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The [sup 14]C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with [sup 14]C increased after 42 hr and remained relatively constant thereafter.
Posted in:

New Frontiers of Cancer Causation

Also detailed are public attitudes toward cancer, as well as attitudes of professionals in cancer research. The volume concludes with some brief considerations from speakers and participants. Annotation copyright by Book News, Inc.

Author: Iversen

Publisher: CRC Press

ISBN: 1560322519

Category: Medical

Page: 444

View: 299

Download →

Proceedings of the Second International Conference on Theories of Carcinogenesis, held in Oslo, Norway, August 1992. The papers, which discuss principles and theories rather than experimental setups and results, cover a wide range of topics, including cell proliferation, metastasis, oncogenes, carcinogens, genetic alterations, viruses, immunology, and radiation. Also detailed are public attitudes toward cancer, as well as attitudes of professionals in cancer research. The volume concludes with some brief considerations from speakers and participants. Annotation copyright by Book News, Inc., Portland, OR
Posted in:

Molecular Determinants of Radiation Response

Given the importance of therapies that induce DNA injury in the management of human disease, this book is timely and relevant for basic and translational researchers, as well as clinicians alike.

Author: Theodore L. DeWeese

Publisher: Springer

ISBN: 1441980458

Category: Medical

Page: 276

View: 597

Download →

Molecular Determinants of Radiation Response includes chapters by expert authors who detail the present understanding of key DNA damage response pathways and proteins. The chapters include comprehensive discussions on where and how specific alterations in function of these pathways and proteins result in substantive modifications of cellular response to DNA injury. Given the importance of therapies that induce DNA injury in the management of human disease, this book is timely and relevant for basic and translational researchers, as well as clinicians alike.
Posted in:

Technologies for Detection of DNA Damage and Mutations

This book provides a collection of techniques that are useful in mutagenesis research. The book is divided into three parts. In Part I, methods for DNA damage and repair analysis are provided.

Author: G.P. Pfeifer

Publisher: Springer Science & Business Media

ISBN: 9781489903013

Category: Science

Page: 441

View: 204

Download →

Man-made carcinogens, natural genotoxic agents in the environment, as well as ionizing and ultraviolet radiation can damage DNA and are a constant threat to genome integrity. Throughout the evolution oflife, complex DNA repair systems have developed in all living organisms to cope with this damage. Unrepaired DNA lesions can promote genetic alterations (mutations) that may be linked to an altered phenotype, and, if growth-controlling genes are involved, these mutations can lead to cell transformation and the development of malignant tumors. Proto oncogenes and tumor suppressor genes may be critical targets for DNA damaging agents. In a number of animal model systems, correlations between exposure to a carcinogen, tumor develop ment, and genetic changes in tumor DNA have been established. To understand mutagenesis processes in more detail at the molecular level, we need to know the type and frequency of DNA adducts within cells, their distribution along genes and specific DNA sequences, as well as the rates at which they are repaired. We also need to know what types of mutations are produced and which gene positions are most prone to mutagenesis. This book provides a collection of techniques that are useful in mutagenesis research. The book is divided into three parts. In Part I, methods for DNA damage and repair analysis are provided.
Posted in:

Chromosomal Alterations

In: Burns FJ, Upton AC, Silini, G (eds) Radiation Carcinogenesis and DNA Alterations. NATO ASI Series, Series A, Life Sciences 124. Plenum New York pp 573-581 Moorhead PS, Nowell PC, Mellman WJ, Battips DM, Hungerford DA (1960) ...

Author: Günter Obe

Publisher: Springer Science & Business Media

ISBN: 9783642788871

Category: Science

Page: 402

View: 174

Download →

Due to sensitive molecular biological techniques, our understanding of chromosomal aberrations is steadily increasing. Provided here is a review of basic and applied aspects of the field. Chromosome structure, induction of DNA lesions by different clastogenic agents and their repair, induction of aberrations by agents which affect specific sequences in the DNA, and factors affecting induction and yield of chromosomal aberrations are covered. Further, topics such as automation of aberration scoring, problems associated with using chromosomal aberrations and micronuclei in population monitoring and the importance of chromosomal aberration assays in mutagenicity testing of chemicals are included.
Posted in:

Biological Effects and Physics of Solar and Galactic Cosmic Radiation

Lavi, S., and Etkin, S., 1981, Carcinogen-mediated induction of SV40 DNA synthesis in SV450 transformed Chinese ... in mammalian cells after exposure to ionizing radiation and UV, in: "Radiation carcinogenesis and DNA alterations", ...

Author: Charles E. Swenberg

Publisher: Springer Science & Business Media

ISBN: 9781461529187

Category: Science

Page: 352

View: 181

Download →

Space missions subject human beings or any other target of a spacecraft to a radiation environment of an intensity and composition not available on earth. Whereas for missions in low earth orbit (LEO), such as those using the Space Shuttle or Space Station scenario, radiation exposure guidelines have been developed and have been adopted by spacefaring agencies, for exploratory class missions that will take the space travellers outside the protective confines of the geomagnetic field sufficient guidelines for radiation protection are still outstanding. For a piloted Mars mission, the whole concept of radiation protection needs to be reconsidered. Since there is an increasing interest ci many nations and space agencies in establishing a lunar base and lor exploring Mars by manned missions, it is both, timely and important to develop appropriate risk estimates and radiation protection guidelines which will have an influence on the design and structure of space vehicles and habitation areas of the extraterrestrial settlements. This book is the result of a multidisciplinary effort to assess the state of art in our knowledge on the radiation situation during deep space missions and on the impact of this complex radiation environment on the space traveller. ]t comprises the lectures by the faculty members as well as short contributions by the students given at the NATO Advanced Study Institute "Biological Effects and Physics of Solar and Galactic Cosmic Radiation" held in Armacao de Pera, Portugal, 12-23 October, 1991.
Posted in:

Radiosensitivity Profiles from a Panel of Ovarian Cancer Cell Lines Exhibiting Genetic Alterations in P53 and Disparate DNA dependent Protein Kinase Activities

The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood.

Author:

Publisher:

ISBN: OCLC:727182292

Category:

Page:

View: 907

Download →

The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.
Posted in:

Oncogenes and Carcinogenesis

This book will mainly focus on the expressions of different oncogenes in breast, colon, and lung cancers.

Author: Pinar Erkekoglu

Publisher: BoD – Books on Demand

ISBN: 9781789851717

Category: Medical

Page: 106

View: 784

Download →

Oncogenes are mutated and/or overexpressed at high levels in tumor cells. Tumors of the lung, breast, pancreas, and colon may display specific oncogenetic features. These tumors have been largely associated with exposure to environmental carcinogens and a variety of biological agents, including viruses. These carcinogens can induce specific genetic and epigenetic alterations in these tissues, leading to aberrant functioning of oncogenes and tumor suppressor genes. On the microRNAs (miRNAs) there are significant modifiers of both transcription and translation of oncogenes in carcinogenesis. In the last 50 years, several oncogenes and microRNAs related to these oncogenes have been identified in different types of human cancers. It is now clear that high expression of oncogenes, DNA damage response, and regulation of the cell cycle are related to the circadian clock. This book will mainly focus on the expressions of different oncogenes in breast, colon, and lung cancers. Moreover, readers will gain qualified scientific knowledge of the alterations in miRNAs in different types of cancers and the effects of the circadian clock on the expression of oncogenes in carcinogenesis.
Posted in:

Aging Carcinogenesis and Radiation Biology

The covalent attachment to deoxyribonucleic acid in vivo of a large number of different types of chemical compounds (both normal cellular constituents such as proteins and amino acids, and also exogenous compounds such as drugs, carcinogens ...

Author: Kendric Smith

Publisher: Springer

ISBN: 0306309114

Category: Medical

Page: 561

View: 583

Download →

The covalent attachment to deoxyribonucleic acid in vivo of a large number of different types of chemical compounds (both normal cellular constituents such as proteins and amino acids, and also exogenous compounds such as drugs, carcinogens, etc. ) have been shown to exert profound effects upon cells. Four research activi ties, formerly considered to be totally independent, relate to this problem of nucleic acid adducts--(1) normal covalent attachment of DNA to membranes, protein linkers in chromosomes, etc. ; (2) the roles of radiation and chemical enhancement of DNA adduct formation in cell killing and mutagenesis. (A related field is the use of known cross-linking reactions to gain information on structural associations in macromolecular complexes. ); (3) the relevance of DNA adducts to chemical and radiation carcinogenesis; (4) the rele vance of DNA adducts to the cross-linking theory of cellular aging. (1) There are numerous examples of normal linkages between DNA and protein, e. g. , DNA-membrane attachment sites, protein linkers in chromosomes, amino acids covalently linked to DNA as a function of growth conditions, and gene regulation by non-covalently bound proteins. A summary of data on natural adducts to DNA thus serves to introduce the subject of the radiation and chemical enhancement of DNA adduct formation. (2) In the past, radiation biology has been concerned mainly with trying to understand the radiation chemistry of purified DNA, and the biological effects and repair of these radiation-induced alterations when produced in cellular DNA.
Posted in: