Mechanism-based cancer prevention approaches: Targets, examples, and the use of transgenic mice

Stephen D. Hursting, Thomas J Slaga, Susan M. Fischer, John DiGiovanni, James M. Phang

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Humans are exposed to a wide variety of carcinogenic insults, including endogenous and man-made chemicals, radiation, physical agents, and viruses. The ultimate goal of carcin genesis research is to elucidate the processes involved in the induction of human cancer so that interventions may be developed to prevent the disease, either in the general population or in susceptible subpopulations. Progress to date in the carcinogenesis field, particularly regarding the mechanisms of chemically induced cancer, has revealed several points along the carcinogenesis pathway that may be amenable to mechanism-based prevention strategies. The purpose of this review is to examine the basic mechanisms and stages of chemical carcinogenesis, with an emphasis on ways in which preventive interventions can modify those processes. Possible ways of interfering with tumor initiation events include the following: i) modifying carcinogen activation by inhibiting enzymes responsible for that activation or by direct scavenging of DNA-reactive electrophiles and free radicals; ii) enhancing carcinogen detoxification processes by altering the activity of the detoxifying enzymes; and iii) modulating certain DNA repair processes. Possible ways of blocking the processes involved in the promotion and progression stages of carcinogenesis include the following: i) scavenging of reactive oxygen species; ii) altering the expression of genes involved in cell signaling, particularly those regulating cell proliferation, apoptosis, and differentiation; and iii) decreasing inflammation. In addition, the utility for mechanism-based cancer prevention research of new animal models that are based on the overexpression or inactivation of specific cancer-related genes is examined.

Original languageEnglish (US)
Pages (from-to)215-225
Number of pages11
JournalJournal of the National Cancer Institute
Volume91
Issue number3
StatePublished - Feb 3 1999
Externally publishedYes

Fingerprint

Transgenic Mice
Carcinogenesis
Carcinogens
Neoplasms
Enzyme Activation
Neoplasm Genes
Research
DNA Repair
Free Radicals
Cell Differentiation
Reactive Oxygen Species
Animal Models
Cell Proliferation
Radiation
Apoptosis
Viruses
Inflammation
Gene Expression
DNA
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mechanism-based cancer prevention approaches : Targets, examples, and the use of transgenic mice. / Hursting, Stephen D.; Slaga, Thomas J; Fischer, Susan M.; DiGiovanni, John; Phang, James M.

In: Journal of the National Cancer Institute, Vol. 91, No. 3, 03.02.1999, p. 215-225.

Research output: Contribution to journalArticle

Hursting, Stephen D. ; Slaga, Thomas J ; Fischer, Susan M. ; DiGiovanni, John ; Phang, James M. / Mechanism-based cancer prevention approaches : Targets, examples, and the use of transgenic mice. In: Journal of the National Cancer Institute. 1999 ; Vol. 91, No. 3. pp. 215-225.
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