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Genotoxicity, Teratogenicity and Mutagenicity of Sulfur Mustard Poisoning

  • Effat BehravanEmail author
  • Mitra Asgharian Rezaee
Chapter

Abstract

Sulfur Mustard (SM) or mustard gas is the most widely used chemical weapons throughout the history. It has been used in World War 1 and recently in Iran-Iraq conflict. Disabilities produced by SM are continuing problems and various cancers as a consequence of SM exposure were reported. Different in vitro and in vivo studies showed DNA damage and mutations following sulfur mustard exposure. These findings along with the other reported delayed complications as cancer following SM toxicity, suggest instability in the genetic system. The most accepted theory of SM toxicity is alkylation reactions with DNA, RNA and proteins in the cell. DNA is the main target for SM toxicity and DNA cross links and adducts constitute 15 % and 85 % of DNA damages respectively. Several studies have documented the mutagenic effects of SM in mammalian cells, in vivo and in vitro test systems. Measurement of DNA damage, measurement of proteins involved in DNA damage and repair signalling, measurement of markers of oxidative stress and evaluation of chromosomal aberration are among the most important tests for evaluating of SM genotoxicity. There is no treatment for SM toxicity yet, therefore, increasing our knowledge about the mechanisms of SM genotoxicity, would help us better understanding about prevention and treatment of SM toxicity in human. Few studies are available regarding the reproductive effects of SM in animals and humans and the results are controversial.

Keywords

Sulfur Mustard Genotoxicity DNA damage Telomere Chromosomal aberration 

Notes

Glossary

Adduct

An adduct is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product.

Adenosine triphosphate (ATP)

ATP is a nucleoside triphosphate used in cells as a coenzyme and transports chemical energy within cells for metabolism.

Alkylation

The attachment of an alkyl group to an organic compound, usually by the addition or substitution of a hydrogen atom or halide group

Apoptosis

A natural process of self-destruction by degradative enzymes in certain cells. Also called programmed cell death.

Carcinogen

A substance or agent that can cause cancer.

Cell cycle

The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication (replication).

Chemical weapon

A chemical agent or toxin, such as mustard gas, lewisite, or sarin, that has been prepared for release on the battlefield or within a civilian population in sufficient concentration to cause widespread illness or death.

Chromosomal aberration

A chromosomal aberration reflects on a typical number of chromosomes or a structural abnormality in one or more chromosomes.

Cross-link

A cross-link is a bond that links one polymer chain to another. They can be covalent bonds or ionic bonds.

DNA

Deoxyribonucleic acid (DNA) is a molecule that encodes the genetic instructions used in the development and functioning of all known living organisms.

DNA fragmentation

The breaking of a (DNA) into smaller parts.

DNA replication

DNA replication is the process of producing two identical copies from one original DNA molecule.

Electrophile

An electron-deficient chemical compound or group that is attracted to electrons and tends to accept electrons.

Eukaryote

A domain of organisms having cells, each with a distinct nucleus within the genetic material is contained.

Genotoxicity

Genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer.

Glutathione

A molecule that acts as a co-enzyme in cellular oxidation-reduction reactions.

Leukemia

Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called “blasts”.

Methylation

The addition of a methyl group to a cytosine residue on double- stranded DNA, a process which plays a major role in regulating gene expression.

Mutation

A change in the nucleotide sequence of the genome of an organism or virus, sometimes resulting in the appearance of a new character or trait not found in the parental type.

Nicotinamide adenine dinucleotide (NAD)

Nicotinamide adenine dinucleotide is a coenzyme and signaling molecule, whose oxidized form is NAD+.

Oxidative stress

Increased oxidant production in animal cells characterized by the release of free radicals and resulting in cellular degeneration.

P53

P53 is a tumor suppressor protein that is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer.

Poly (ADP-ribose) polymerase (PARP)

PARP is a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death.

Prokaryote

The prokaryotes are a group of organisms whose cells lack a membrane-bound nucleus (karyon).

Recombination

Several processes by which genetic material of different origins becomes combined. It most commonly occurs between the two sets of parental chromosomes during production of germ cells

RNA

Ribonucleic acid (RNA) is a ubiquitous family of large biological molecules that perform multiple vital roles in the coding, decoding, regulation, and expression of genes.

Sister chromatid exchange

Sister chromatid exchange (SCE) is the exchange of genetic material between two identical sister chromatids. Used as a mutagenic testing of many products.

Spermatogenesis

The process by which sperm develop to become mature sperm, capable of fertilizing an ovum.

Sulfur mustard

A class of related cytotoxic and vesicant chemical warfare agents with the ability to form large blisters on the exposed skin and in the lungs

Telomere

A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes.

Teratogen

Any agent or factor that induces or increases the incidence of abnormal prenatal development.

Transcription

Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA by the enzymes, RNA polymerase.

Tumor promoter

A substance that has no intrinsic carcinogenic potential, but which, when applied repeatedly, amplifies cancer-inducing effects of other (initiator) substances.

Tumor suppressor gene

A gene that its function is to limit cell proliferation and loss of function leads to cell transformation and tumor growth. Also called antioncogene.

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical SciencesMashhadIran
  2. 2.Department of Toxicology and Pharmacology, Faculty of PharmacyKerman University of Medical SciencesKermanIran

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