Standard Article

Mutagenesis

Genetic Toxicology, Oncogenesis, Developmental and Reproductive Toxicology

  1. Anthony Lynch

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat074

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Lynch, A. 2009. Mutagenesis. General, Applied and Systems Toxicology. .

Author Information

  1. Head, Investigative Genetic Toxicology, GalxoSmithKlyne Research and Development, Ware, Herefordshire, UK

Publication History

  1. Published Online: 15 DEC 2009

Abstract

There is overwhelming evidence that inherited mutational changes in humans are responsible for a significant proportion of genetically determined diseases and congenital (heritable) malformations. In addition, the accumulation of somatic cell mutations is known to be implicated in cancer, and to some extent in other multifactorial diseases, for example heart disease. Thus the integrity of human DNA is essential for the future of the species and the health of its individuals. DNA damage may be induced by errors in DNA replication/repair, exposure to endogenous mutagens (such as reactive oxygen species) or by environmental factors. Novel chemicals/consumer products/drugs represent an additional potential source of damage to DNA, and so appropriate testing is required to minimise the risk of genotoxicity. The discipline of genetic toxicology as applied to chemicals/consumer product/drug development exists to achieve this aim. An additional role of genetic toxicology is the assessment of the relative risk arising from exposure to carcinogens, particularly those which are DNA reactive. The aims of this chapter are to provide an overview of the organization of the genetic material, DNA, and describe the mechanisms by which mutations arise in DNA (mutagenicity) and the links between mutations and the role they play in hereditary diseases and cancer; and also other multifactorial diseases and ageing. The chapter goes on to describe the discipline of genetic toxicology, its history and the development of assays for the measurement of mutations in model organisms. It culminates in a description of the standard regulatory battery of in vitro and in vivo tests used to assess the potential genotoxic liability of a novel test agent, plus additional supplementary tests that can be used to investigate further the underlying biological mechanisms resulting in genotoxicity. The chapter continues with a discussion on data interpretation and current concepts of risk assessment in genetic toxicology, and concludes with an outline of the challenges faced by genetic toxicology in the new millennium, and describes developments within the discipline to meet these challenges.

Keywords:

  • genetics;
  • gene mutation;
  • mutagenesis;
  • hereditary disease;
  • cancer;
  • carcinogenesis;
  • ageing;
  • genetic toxicology;
  • DNA;
  • DNA damage;
  • clastogenicity;
  • aneuploidy;
  • hazard identification;
  • risk assessment;
  • chemical testing