Effect on liver tumor growth in rats of allopurinol and 5-fluorouracil in combination with hepatic artery ligation

Summary Rats with an experimental solitary liver tumor of a nitrosoguanidine-induced colonic adenocarcinoma were subjected to hepatic artery ligation (HAL) alone or in combination with 5-fluorouracil (5-FU) in three different doses, with or without the addition of allopurinol. The drugs were injected i.p. on 3 consecutive days before or after the HAL procedure. HAL alone significantly reduced the tumor growth compared with the control procedure (P<0.001). This observation was correlated with a significantly prolonged survival for the ligated animals (P<0.01). The administration of a low dose of 5-FU (15 mg/kg per day) in combination with allopurinol (100 mg/kg per day) enhanced tumor growth compared with that in animals treated with 5-FU only (P<0.01) or nontreated animals (P<0.05). A significant increase in survival was observed in animals given a high dose of 5-FU (60 mg/kg per day) after HAL compared with nontreated animals (P<0.001) as well as animals subjected to HAL alone (P<0.02). All animals receiving more than 15 mg/kg per day 5-FU before HAL succumbed within 10 days. The addition of allopurinol did not protect the animals against this mortality. These observations indicate that the effect of HAL followed by 5-FU is dose-dependent and that, at least in this treatment modality, allopurinol does not modulate the toxicity of 5-FU.This study was supported by Swedish Medical Research Council grants B85-17X-07184-01A, B86-04X-07155-02B, and B87-04X-07155-03A and the Wellcome Foundation