Arachidonic acid metabolism as a reporter of skin irritancy and target of cancer chemoprevention.
Keratinocytes respond to skin irritation and injury by cytokine release and a rapid but transient activation of arachidonic acid metabolism along both the cyclooxygenase and lipoxygenase pathways. In the first part of this article results are reviewed indicating that the release of pro-inflammatory mediators such as eicosanoids and interleukin-1 from keratinocytes provides a suitable in vitro parameter of irritancy. Based on this response an assay system has been established which may partially replace animal tests such as the Draize test. A permanent overactivation of arachidonic acid metabolism appears to be a driving force of tumor development in both experimental animals and man. Inhibition of the enzymes involved (such as cyclooxygenases by nonsteroidal antiinflammatory drugs) provides, therefore, a powerful and promising measure of cancer chemoprevention. The state of the art in this rapidly developing field is briefly reviewed in the second part of this article.
Marks
F
F
Deutsches Krebsforschungszentrum (German Cancer Research Center), Forschungsschwerpunkt Tumorzellregulation, Heidelberg.
Fürstenberger
G
G
Müller-Decker
K
K
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000378:metabolism*; D018890:Chemoprevention / Q000379:methods; D017453:Dermatitis, Irritant / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control*; D014116:Toxicology / Q000379:methods
D016588:Anticarcinogenic Agents; D016718:Arachidonic Acid