PROSTAGLANDINS PROTECT AGAINST MURINE HAIR INJURY PRODUCED BY IONIZING-RADIATION OR DOXORUBICIN

Several years ago we showed that prostaglandins (PGs) are potent radio protective agents. To investigate further the potential use of these c ompounds we employed quantitative measures of murine hair loss and reg rowth to assess the effects of PG administration before multi-dose fra ctionated radiation exposures. We compared these results with findings utilizing the thiol compounds WR-2721 or WR-1065, the ''gold standard '' laboratory radioprotectors. Three weeks after systemic administrati on of 16-16 dm PGE2 (Upjohn Company) or WR-272 1, given 1 h before eac h dose of 2-4.5 Gy per fraction for 10-15 fractions, regrowing hair co unts increased up to 100% compared to irradiated-only skin sites. The thiol compound effects were slightly superior to the PG effects in the se studies. Local applications of 16-16 dm PGE2 or WR-1065 given 15 mi n before each radiation fraction also enhanced post-radiation hair reg rowth, although though systemic administration of either agent was mor e effective than the topical route. We also evaluated possible protect ive effects of PGs given before doxorubicin, measuring murine hair los s 1 week after parenteral injections of the drug. Five daily doses of doxorubicin, 0.1 mg/25 g animal, reduced the number of hairs in a 4.42 mm2 area of skin from 241 +/- 5 (controls) to 144 +/- 3. Misoprostol (G.D. Searle & Co.), 25 mug/mouse, applied locally 2 h before each dos e of doxorubicin, resulted in 213 +/- 8 residual hairs. We conclude th at clinical use of these compounds may provide significant protection of hair follicles and possibly other normal tissues (skin; oral, recta l, and bladder mucosa) lying within a radiation field or in patients t reated with chemotherapeutic agents. Further assessment of possible tu mor protection effects are needed, however.