کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2581162 1561647 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Proposed mode of action of benzene-induced leukemia: Interpreting available data and identifying critical data gaps for risk assessment
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Proposed mode of action of benzene-induced leukemia: Interpreting available data and identifying critical data gaps for risk assessment
چکیده انگلیسی

Mode of action is defined as a series of key biological events leading to an observed toxicological effect (for example, metabolism to a toxic entity, cell death, regenerative repair and tumors). It contrasts with mechanism of action, which generally involves a detailed understanding of the molecular basis for an effect.A framework to consider the weight of evidence for hypothesized modes of action in animals and their relevance to humans, has been widely adopted and used by government agencies and international organizations. The framework, developed and refined through its application in case studies for principally non-DNA-reactive carcinogens, has more recently been extended to DNA-reactive carcinogens, non-cancer endpoints and different life stages. In addition to increasing transparency, use of the framework promotes consistency in decision-making concerning adequacy of weight of evidence, facilitates peer input and review and identifies critical research needs.The framework provides an effective tool to facilitate discussion between the research and risk assessment communities on critical data gaps, which if filled, would permit more refined estimates of risk.As a basis for additionally coordinating and focusing research on critical data gaps in a risk assessment context, five key events in the mode of action for benzene-induced leukemia are proposed: (1) benzene metabolism via Cytochrome P450, (2) the interaction of benzene metabolites with target cells in the bone marrow, (3) formation of initiated, mutated target cells, (4) selective proliferation of the mutated cells and (5) production of leukemia. These key events are considered in a framework analysis of human relevance as a basis to consider appropriate next steps in developing research strategies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 184, Issues 1–2, 19 March 2010, Pages 279–285
نویسندگان
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