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Nitric Oxide and Genomic Stability

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Nitric Oxide and Cancer: Pathogenesis and Therapy

Abstract

Epidemiological evidence accumulating over the years has provided a positive correlation between cancer incidence and chronic inflammation. Regardless of etiology, inflammatory conditions are characterized by overexpression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide/reactive nitrogen species (NO/RNS) in epithelial and inflammatory cells at the site of carcinogenesis. NO/RNS produced in infected and inflamed tissues can contribute to the process of carcinogenesis by different mechanisms. In this chapter, we discuss NO/RNS-dependent mechanisms of genomic instability (GI) and bystander effects. We explain the mechanism of “synthetic lethality” of the NO-donor/PARP-inhibitor combination and its role in sensitization of the cancer cells to DNA-damaging agents. We postulate the “mutator field” theory and the definition of mutagenesis efficacy.

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Abbreviations

BDD:

Bystander DNA damage

BER:

Base excision repair

BRCA1:

Breast cancer type 1 susceptibility protein;

DSB:

Double-strand brake

EADC:

Esophageal adenocarcinoma

eNOS:

Endothelial nitric oxide synthase

GERD:

Gastro-esophageal reflux disease

HCC:

Hepatocellular carcinoma

HRND:

High concentration range of NO-donors

IBDs:

Inflammatory bowel diseases

iNOS:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharides

MN:

Micronuclei

MRND:

Moderate concentration range of NO-donors

NHEJ:

Non-homologous end joining

NHL:

Non-Hodgkin lymphoma

NO/RNS:

Nitric oxide/reactive nitrogen species

OLP:

Oral lichen planus

OSCC:

Oral squamous cell carcinoma

OV:

Opisthorchis viverrini

PARP1:

Poly(ADP-ribose) polymerase 1

PC:

Prostate cancer

ROS:

Reactive oxygen species

SNP:

Single nucleotide polymorphisms

SSB:

Single-strand breaks

SSF:

Stress signal factors

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Acknowledgments

The present work was supported by National Institutes of Health Grant R01 CA90881.

Conflict Statement

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Radiation Oncology, VCU/Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Rm. 381, 2398, Richmond, VA, USA

    Vasily A. Yakovlev

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  1. Vasily A. Yakovlev
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Correspondence to Vasily A. Yakovlev .

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Editors and Affiliations

  1. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California of Los Angeles, Los Angeles, California, USA

    Benjamin Bonavida

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Yakovlev, V. (2015). Nitric Oxide and Genomic Stability. In: Bonavida, B. (eds) Nitric Oxide and Cancer: Pathogenesis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-13611-0_2

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