AMELIORATION OF BOTH EARLY AND LATE RADIATION-INDUCED DAMAGE TO PIG SKIN BY ESSENTIAL FATTY-ACIDS

Purpose: To evaluate the possible role of essential fatty acids, speci fically gamma-linolenic and eicosapentaenoic acid, in the amelioration of early and late radiation damage to the skin. Methods and Materials : Skin sites on the flank of 22-25 kg female large white pigs were irr adiated with either single or fractionated doses (20 F/28 days) of bet a-rays from 22.5 mm diameter Sr-90/Y-90 plaques at a dose rate of simi lar to 3 Gy/min. Essential fatty acids were administered orally in the form of two 'active' oils, So-1100 and So-5407, which contained gamma -linolenic acid and a mixture of that oil with eicosapentaenoic acid, respectively. Oils (1.5-6.0 ml) were given daily for 4 weeks prior, bo th 4 weeks prior and 10-16 weeks after, or in the case of one single d ose study, just for 10 weeks after irradiation. Control animals receiv ed a 'placebo' oil, So-1129, containing no gamma linolenic acid or eic osapentaenoic acid over similar time scales before and after irradiati on. Acute and late skin reactions were assessed visually and the dose- related incidence of a specific reaction used to compare the effects o f different treatment schedules. Results: A reduction in the severity of both the early and late radiation reactions in the skin was only ob served when 'active' oils were given over the time course of the expre ssion of radiation damage. Prior treatment with oils did not modify th e radiation reaction. A 3.0 ml daily dose of either So-1100 or So-5407 given prior to, but also after irradiation with single and fractionat ed doses of beta-rays produced the most significant modification to th e radiation reactions, effects consistent with dose modification facto rs between 1.06-1.24 for the acute reactions of bright red erythema an d/or moist desquamation, and of 1.14-1.35 for the late reactions of du sky/mauve erythema and dermal necrosis. There was the strong suggestio n of an effect produced by the 'placebo' oil, So-1129, after higher da ily doses of oil. Conclusions: Essential fatty acids can modulate norm al tissue reactions when given over the time when radiation damage is normally expressed. Dose modification factors suggest that a greater t han or equal to 10% higher dose is required to produce the same level of normal tissue injury. Clinical application of selected essential fa tty acids at appropriate doses may lead to a significant increase in t he therapeutic gain in patients treated for cancer by radiotherapy.