Tumour Site Concordance And Mechanisms Of Carcinogenesis

This Scientific Publication reviews the information on cancer sites and mechanistic events for the more than 100 agents classified in Group 1 (carcinogenic to humans) by the IARC Monographs Program. This category of agents is diverse and includes chemicals and chemical mixtures; occupations; metals, dusts, and fibres; radiation; viruses and other biological agents; personal habits; and pharmaceuticals. For the Group 1 agents, there were cross-cutting questions about the relevance to humans of certain cancer sites or mechanistic pathways in animals. This publication is based on a systematic identification and comparison of the cancer sites observed in humans and those observed in experimental animals, and a compilation of mechanistic events for agents known to cause cancer in humans. Relevant information was analyzed on all the agents classified in Group 1 in Monographs up to and including Volume 109, most of which are reviewed in Volume 100A-F. A database of tumor sites seen in humans and animals was used to examine the degree of concordance by use of an anatomically based tumor classification scheme. The analysis of mechanistic aspects of the IARC Group 1 agents focused on 10 key characteristics of human carcinogens developed during the course of this work. Genotoxicity was the most prevalent mechanistic characteristic, consistent with the process of carcinogenesis necessarily involving genomic changes. The IARC concordance database represents a useful source of information for comparing animal and human data with respect to the tumors caused in different species. The results of the mechanistic analysis can provide a basis for future efforts to categorize mechanistic data for carcinogens through a systematic review process. These reviews and analyses were discussed during a two-part Workshop on Tumour Site Concordance and Mechanisms of Carcinogenesis convened by IARC. This Scientific Publication is the report of that Workshop and of subsequent work by the participants, both individually and collectively. This publication also presents a statement of consensus among the Workshop participants, which summarizes the main findings and their implications for human cancer risk assessment.

This Scientific Publication reviews the information on cancer sites and mechanistic events for the more than 100 agents classified in Group 1 (carcinogenic to humans) by the IARC Monographs Programme. This category of agents is diverse and includes chemicals and chemical mixtures; occupations; metals, dusts, and fibres; radiation; viruses and other biological agents; personal habits; and pharmaceuticals. For the Group 1 agents, there were cross-cutting questions about the relevance to humans of certain cancer sites or mechanistic pathways in animals. This publication is based on a systematic identification and comparison of the cancer sites observed in humans and those observed in experimental animals, and a compilation of mechanistic events for agents known to cause cancer in humans. Relevant information was analysed on all the agents classified in Group 1 in Monographs up to and including Volume 109, most of which are reviewed in Volume 100A-F. A database of tumour sites seen in humans and animals was used to examine the degree of concordance by use of an anatomically based tumour classification scheme. The analysis of mechanistic aspects of the IARC Group 1 agents focused on 10 key characteristics of human carcinogens developed during the course of this work. Genotoxicity was the most prevalent mechanistic characteristic, consistent with the process of carcinogenesis necessarily involving genomic changes. The IARC concordance database represents a useful source of information for comparing animal and human data with respect to the tumours caused in different species. The results of the mechanistic analysis can provide a basis for future efforts to categorize mechanistic data for carcinogens through a systematic review process. These reviews and analyses were discussed during a two-part Workshop on Tumour Site Concordance and Mechanisms of Carcinogenesis convened by IARC. This Scientific Publication is the report of that Workshop and of subsequent work by the participants, both individually and collectively. This publication also presents a statement of consensus among the Workshop participants, which summarizes the main findings and their implications for human cancer risk assessment.

but also the possibility of intervention in specific stages. In Human behavior, including stress and other factors, plays an important role in neoplasia, although too little is known addition, variables which affect cancer development as well on the reasons for such development. Carcinogens, which as some endogenous factors can be better delineated help initiate the neoplastic process, may be either synthetic through such investigations. The topics of this volume encompass premalignant non or naturally-occurring. Cancer causation may be ascribed to invasive lesions, species-specific aspects of carcinogenicity, certain chemicals, physical agents, radioactive materials, viruses, parasites, the genetic make-up of the organism, and radiation, viruses, a quantum theory of carinogenesis, onco bacteria. Humans, eumetazoan animals and vascular plants genes, and selected environmental carcinogens. are susceptible to the first six groups of cancer causes, whe reas the last group, bacteria, seems to affect only vascular plants. Neoplastic development may begin with impairment ofJmdy defenses by a toxic material (carcinogen) which acts as an initiator, followed by promotion and progression to an overt neoplastic state. Investigation of these processes Series Editor Volume Editor allows not only a better insight into the mechanism of action Hans E. Kaiser Elizabeth K. Weisburger vii ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E. H. Krokowski.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.

This volume will provide a contemporary account of advances in chemical carcinogenesis. It will promote the view that it is chemical alteration of the DNA that is a route cause of many cancers. The multi-stage model of chemical carcinogenesis, exposure to major classes of human carcinogens and their mode-of-action will be a focal point. The balance between metabolic activation to form biological reactive intermediates and their detoxification, ensuing DNA-lesions and their repair will be profiled. It will describe the chemical changes that occur in DNA that result from endogenous insults including epigenetic changes that lead to gene silencing. It will describe major mechanisms of mutagenesis, affects on tumor suppressor genes and proto-oncogenes, and how cell-cycle check points can be by-passed by the "stealth-like" properties of chemical carcinogens. Environmental agents that can promote tumor formation will be discussed. The monograph will have wide appeal as a knowledge base for graduate students, post-doctoral fellows and faculty interested in this aspect of cancer causation and research.

This comprehensive multidisciplinary book examines all aspects of cancers of the mouth and oropharynx with the aim of equipping advanced students and practitioners in the early stages of specialist training with an up-to-date guide and reference. A multinational team of authors – all experts in the field of oral oncology – provide illuminating contributions on the full range of relevant topics: epidemiology, risk factors, clinical features, staging and prognostic factors, pathology, diagnostic techniques, disease prevention, surgery, radiotherapy, and chemotherapy. Molecular biology, molecular targeted therapies for advanced cases, and future diagnostic and prognostic applications of new technologies also receive careful attention. In providing a wealth of essential information and guidance in a practical format, the book will be a superb asset for senior graduate students in dentistry and specialist trainees in head and neck oncology. It will also be of high value for the many physicians, surgeons, pathologists, dentists, and specialists involved in the prevention, diagnosis, and management of squamous cell carcinomas of the oral cavity and oropharynx.

Learn to implement effective control measures for mutagenic impurities in pharmaceutical development In Mutagenic Impurities: Strategies for Identification and Control, distinguished chemist Andrew Teasdale delivers a thorough examination of mutagenic impurities and their impact on the pharmaceutical industry. The book incorporates the adoption of the ICH M7 guideline and focuses on mutagenic impurities from both a toxicological and analytical perspective. The editor has created a primary reference for any professional or student studying or working with mutagenic impurities and offers readers a definitive narrative of applicable guidelines and practical, tested solutions. It demonstrates the development of effective control measures, including chapters on the purge tool for risk assessment. The book incorporates a discussion of N-Nitrosamines which was arguably the largest mutagenic impurity issue ever faced by the pharmaceutical industry, resulting in the recall of Zantac and similar drugs resulting from N-Nitrosamine contamination. Readers will also benefit from the inclusion of: A thorough introduction to the development of regulatory guidelines for mutagenic and genotoxic impurities, including a historical perspective on the development of the EMEA guidelines and the ICH M7 guideline An exploration of in silico assessment of mutagenicity, including use of structure activity relationship evaluation as a tool in the evaluation of the genotoxic potential of impurities A discussion of a toxicological perspective on mutagenic impurities, including the assessment of mutagenicity and examining the mutagenic and carcinogenic potential of common synthetic reagents Perfect for chemists, analysts, and regulatory professionals, Mutagenic Impurities: Strategies for Identification and Control will also earn a place in the libraries of toxicologists and clinical safety scientists seeking a one-stop reference on the subject of mutagenic impurity identification and control.