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 administered orally for the prevention (PRG) and treatment (TRG) of benzo(a)pyrene (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 groups. 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-injected group, a tricapryline-injected group and a BaP-injected and treated by the low dose combination group. Results revealed that the low dose 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 addition, found in autopsy and histological examination in the low dose combination (PRG and TRG) and the high dose TRG groups. The high dose combination groups manifested a significant prolongation of the mean survival 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 increased number of double tumor formation in the PRG group. Urine MDA increased significantly in animals injected by BaP during the first 10 days and since the 90th day (formation of palpable tumors) after injection, in relation to control and tricapryline-injected groups. Complete prevention of urine MDA-increased values was obtained in BaP-injected and treated by the low dose combination animals. Results indicate that high 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 sufficient prevention and treatment of malignant diseases. (C) 1997 Elsevier Science Ireland Ltd.