p53 Mutation Load

A Molecular Linkage to Carcinogen Exposure and Cancer
  • S. Perwez Hussain
  • Curtis C. Harris
Part of the Environmental Science Research book series (ESRH, volume 56)


Normal tissue homeostasis is maintained by the interplay of a number of different genes that control cellular proliferation and cell death. Many of these genes, for example, ras, p53 and Rb,are altered in a variety of human cancers and are implicated in the natural history of human cancer. Several reports have described that each endogenous or exogenous mutagen induces a characteristic pattern of DNA alteration (Greenblatt et al., 1994; Patel et al.,1998), which can be displayed in a mutational spectrum that provides the type, location and frequency of alterations in a gene. The p53 tumor suppressor gene is of particular interest because it is mutated in about half of all cancer types arising in a variety of tissues, and it manifests a high frequency of missense mutations (substitution of an amino acid in the encoded protein) (Hollstein etal., 1991; Levine et al., 1991; Ponder, 1988). The extensive study of p53 mutation spectra has both provided information relevant to human cancer and generated several hypotheses. For example, a p53 mutation spectrum can reflect the DNA damage of a particular carcinogen and aid in defining the biochemical mechanisms responsible for the genetic lesions in DNA that cause human cancer. The frequency and type of p53 mutations can also act as a molecular dosimeter of carcinogen exposure and provide information about the molecular epidemiology of cancer risk. In this article, we will discuss how a characteristic mutation in the p53 tumor suppressor gene can indicate the exposure to a particular mutagen or carcinogen in the environment. In addition, the p.53 gene can be a target to evaluate the mutagenicity of an unknown environmental pollutant, by using human cell cultures and a highly sensitive genotypic mutation assay (Aguilar et al., 1994; Aguilar et al., 1993; Hussain et al., 1994a; Hussain etal., 1994b).


Skin Cancer Human Bronchial Epithelial Cell Cigarette Smoke Condensate Carcinogen Exposure Cell BioI 
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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • S. Perwez Hussain
    • 1
  • Curtis C. Harris
    • 1
  1. 1.Laboratory of Human CarcinogenesisNational Cancer Institute, NIHBethesdaPalästina

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