DOSE-RELATED PREVENTIVE AND THERAPEUTIC EFFECTS OF ANTIOXIDANTS-ANTICARCINOGENS ON EXPERIMENTALLY-INDUCED MALIGNANT-TUMORS IN WISTAR RATS

A combination of antioxidants-anticarcinogens, consisting of vitamins C and E, selenium and 2-mercaptopropionyl glycine (2-MPG), was adminis tered orally for the prevention (PRG) and treatment (TRG) of benzo(a)p yrene (BaP)-induced malignant tumors (leiomyosarcomas), in Wistar rats . In order to evaluate dose-related effects, a low dose vitamin (0.15 g/kg b.w. per day of vit.C and 0.05 g/kg b.w. per day of vit,E) and a high dose (1.5 g/kg b.w. per day of vit.C and 0.5 g/kg b.w. per day of vit.E) combination was administered, in prevention and treatment grou ps. Selenium was administered in doses of 2 mu g/kg b.w. per day and 2 -MPG in 15 mg/kg b.w. per day, in all groups. Daily estimations of 24 h urine volume levels of thiobarbituric acid reacting substances (MDA) were performed in 20 animals, divided into a control group, a BaP-inj ected group, a tricapryline-injected group and a BaP-injected and trea ted by the low dose combination group. Results revealed that the low d ose combination failed to exert any beneficial effect on mean survival time of animals treated either preventitively or therapeutically. An increased number of animals bearing a second (lung) tumor was, in addi tion, found in autopsy and histological examination in the low dose co mbination (PRG and TRG) and the high dose TRG groups. The high dose co mbination groups manifested a significant prolongation of the mean sur vival time of animals; complete remission of tumors developed in 16.8% of the animals in the treatment group and a 5.2% prevention of tumor formation in the preventive group, without any evidence of an increase d number of double tumor formation in the PRG group. Urine MDA increas ed significantly in animals injected by BaP during the first 10 days a nd since the 90th day (formation of palpable tumors) after injection, in relation to control and tricapryline-injected groups. Complete prev ention of urine MDA-increased values was obtained in BaP-injected and treated by the low dose combination animals. Results indicate that hig h doses (megadoses) of the antioxidant-anticarcinogen vitamins C and E in combination with carefully selected other antioxidants possessing supplementary actions, are probably needed in order to achieve a suffi cient prevention and treatment of malignant diseases. (C) 1997 Elsevie r Science Ireland Ltd.