Eicosanoids and radiation.

Abstract

radiotherapy depends on the tolerance of the critical normal tissue within the radiation field. Consequently, any attempt to improve the efficacy of radiotherapy must be aimed at increasing tumour radioresponse and/or reducing normal tissue complications. To achieve this objective, many diverse approaches have been investigated, including modulation of levels of eicosanoids, especially prostaglandins (PCs), in both normal tissues and tumours. Eicosanoids are produced in response to a variety of cellular injuries, and exogenous eicosanoids have been shown to modulate injury induced by a wide array of agents. Therefore, it was logical to infer their involvement in tissue injury by ionising radiation. During the past 20 years, there has been significant research into the role of eicosanoids, primarily PGs, in radiation damage. Attempts have been made to modulate normal tissue damage by administering exogenous PGs or inhibiting endogenous PGs. Other studies have been conducted to increase tumour response to radiation by modulating PG levels in tumours. This overview considers major fmdings on the role of eicosanoids in the expression and modification of radiation damage, with special emphasis on its therapeutic potential. EICOSANOIDS Eicosanoids is a collective term for PGs, thromboxanes (TXs), leucotrienes (LTs), and various hydroxy and hydroperoxy fatty acids. They are metabolites of polyunsaturated fatty acids, such as arachidonic acid, and are produced by virtually all tissues via the cycle-oxygenase (for PGs and TXs) and lipoxygenase (for LTs) pathways. These end products of the arachidonic acid cascade are bioactive substances; for example, there is an array of PGs: PGEi, PGE2, PGF,,, PGD*, PGIz (prostacyclin), etc., each exhibiting different biological actions. It is no wonder then that eicosanoids display an astonishingly wide range of pharmacological, physiological, and pathological effects. They play a regulatory role in many physiological homeostatic processes including immunomodulation, vasomotility (constriction and dilatation) and platelet aggregation, along with regulating