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p53 and Ras Mutations in Cancer and Experimental Carcinogenesis

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Chemical Carcinogenesis

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Cancer is initiated and maintained by the accumulation of numerous mutations in specific genes. Rarely, the mutations are inherited but more commonly they occur via exposure to chemical carcinogens. Mutant genes fall into two categories: tumor suppressors and oncogenes. The most commonly mutated tumor suppressor is p53, while one of the most commonly mutated oncogenes is Ras. p53 induces cell cycle arrest and apoptosis in cells that have undergone DNA damage. Mutations in p53 usually result in inactivation of its normal transcriptional ability, leading to unregulated growth of damaged cells. In contrast, mutations in Ras are activating mutations that lead to increased cell proliferation. Among the more commonly studied carcinogens are polycyclic aromatic hydrocarbons (PAH), which are combustion products found in cigarette smoke, and aflatoxins, which are produced by molds. These are not carcinogenic until metabolically activated to compounds known as ultimate carcinogens, which can damage DNA, leading to mutations. Molecular epidemiology and experimental carcinogenesis with Ras and p53 have led to an understanding of the roles of metabolic activation and genetic selection in cancer.

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Acknowledgements

This work was supported by grants R01 GM48241 and R01 ES015662, and pilot project support from 1P30 ES013508–01 to J.F. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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  1. Centers of Excellence in Environmental Toxicology and Cancer Pharmacology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Jeffrey Field

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  1. Zahidur Abedin
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  2. Sushmita Sen
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  3. Elise Morocco
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  4. Jeffrey Field
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Correspondence to Jeffrey Field .

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  1. School of Medicine, Dept. Pharmacology, University of Pennsylvania, Hamilton Walk 3260, Philadelphia, 19104, Pennsylvania, USA

    Trevor M. Penning

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Abedin, Z., Sen, S., Morocco, E., Field, J. (2011). p53 and Ras Mutations in Cancer and Experimental Carcinogenesis. In: Penning, T. (eds) Chemical Carcinogenesis. Current Cancer Research. Humana Press. https://doi.org/10.1007/978-1-61737-995-6_18

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