BOMBESIN ANTAGONIST PREVENTS CO2 LASER-INDUCED PROMOTION OF ORAL-CANCER

We previously reported that CO2 laser incisions in carcinogen-initiate d fields promoted cancer development and caused release of growth fact ors, Here we examined the quantitative and additive properties of this tumor-promoting event and examined whether this promotion could be nu llified by treatment with a bombesin antagonist, which down-regulates epidermal growth factor receptors, The model used for cancer promotion was the hamster buccal cheek pouch that had been treated with a carci nogen (9,10-dimethyl-1,2-benzanthracene) for 6 weeks, producing premal ignant lesions, These lesions would evolve Into a cancer eventually wi thout further treatment, Promotion was measured both by increased fluo rescence in response to systemically administered Photofrin, measured noninvasively using an in vivo fluorescence photometer, and by the tim ing of appearance of clinical tumors, Laser incisions (0-3) were made into the hamster cheek 1 week apart, or three incisions were done 1 da y apart, Another group of animals received bombesin antagonist RC-3095 for 4 weeks during the time incisions were made, again measuring prom otion, Laser incisions 1 week apart produced additive promotion, where as three incisions 1 day apart were not statistically different from t he group receiving only one incision, RC-3095 treatment completely eli minated the promoting effects of incision and totally stopped promotio n for the 4-week period of treatment, After discontinuing treatment wi th RC-3095, lesion progression resumed at the untreated control rate, This work confirms that the promoting event of a laser incision follow s a comparable time course to release of growth factors after such an incision and that it can be eliminated by treatment with bombesin anta gonists.