ARACHIDONIC-ACID METABOLISM AS A REPORTER OF SKIN IRRITANCY AND TARGET OF CANCER CHEMOPREVENTION

Keratinocytes respond to skin irritation and injury by cytokine releas e 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-l fr om 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 ov eractivation of arachidonic acid metabolism appears to be a driving fo rce of tumor development in both experimental animals and man. Inhibit ion of the enzymes involved (such as cyclooxygenases by nonsteroidal a ntiinflammatory drugs) provides, therefore, a powerful and promising m easure of cancer chemoprevention. The state of the art in this rapidly developing field is briefly reviewed in the second part of this artic le. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.