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Genomic Instability in Carcinogenesis

The Role of Oxidative Stress

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Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

Abstract

Genomic instability is one of the hallmarks of cancer. Several theories have been put forth to ascertain this departure from the normal state as being the driver of tumorigenesis or as its final manifestation. Two such theories, the mutator phenotype hypothesis and the oncogene induced replication stress model, have attempted to resolve this dichotomy. However, the source of the mutations implicit in these theories has remained unaddressed in the context of genomic instability. One likely source is the oxidative stress caused by an uncounterable surge of reactive chemical species like reactive oxygen species (ROS) and reactive nitrogen species (RNS). Such species undergo various chemical reactions with different biomolecules present in the cell, most importantly with the DNA and the proteins involved in the maintenance of the genome, leading to the loss of cellular homeostasis and genomic instability. This chapter aims to explicate how oxidative stress drives genetic instability and thus cancer development through interactions with DNA, proteins, and lipids. It also touches upon the mechanisms the stressed cells employ to reset the homeostasis and how the failure of such means ultimately leads to the loss of genetic integrity and the onset of carcinogenesis.

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Acknowledgment

SN is supported by Early Career Award, Science & Engineering Research Board (SERB)-Dept. of Science and Technology (DST), Govt Of India (File No. ECR/2015/000206) and Grant-in-Aid, Department of Science & Technology and Biotechnology (DSTBT), Govt. of West Bengal (FST/P/S&T/9G-21/2016) and, Extra mural research grant, Science & Engineering Research Board (SERB)-Dept. of Science and Technology (DST), Govt Of India (File No.EMR/2015/001835). SR is supported by University Grants Commission- Junior Research Fellowship (UGC Ref. No.:771/CSIR-UGC NET-2017).

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Authors and Affiliations

  1. Department of Basic and Translational Research, Saroj Gupta Cancer Centre and Research Institute, Kolkata, India

    Somsubhra Nath & Stuti Roy

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  1. Somsubhra Nath
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  2. Stuti Roy
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Editors and Affiliations

  1. Department of Biochemistry and Biophysic, University of Kalyani Department of Biochemistry and Biophysic, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Dept of Veterinary Pathobiology, University of Missouri, College Vet, Columbia, MO, USA

    Bimal K Ray

  3. Saroj Gupta Cancer Centre & Research Ins, Kolkata, India

    Sushanta Roychowdhury

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Nath, S., Roy, S. (2021). Genomic Instability in Carcinogenesis. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_155-1

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  • DOI: https://doi.org/10.1007/978-981-15-4501-6_155-1

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  • Print ISBN: 978-981-15-4501-6

  • Online ISBN: 978-981-15-4501-6

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