DIETARY-FOLATE PROTECTS AGAINST THE DEVELOPMENT OF MACROSCOPIC COLONIC NEOPLASIA IN A DOSE RESPONSIVE MANNER IN RATS

Background and Aims-Diminished folate status is associated with enhanc ed colorectal carcinogenesis. This study investigated the potential ch emopreventive role of dietary folate in the dimethylhydrazine colorect al cancer model. Subjects and Methods-Sprague-Dawley rats were fed die ts containing either 0, 2 (daily dietary requirement), 8 or 40 mg fola te/kg diet for 20 weeks. After five weeks of diet, rats were injected with dimethylhydrazine (44 mg/kg) weekly for 15 weeks. Fifteen weeks a fter the first injection of dimethylhydrazine, all rats were killed. F olate status was determined, and the entire colorectum from each rat w as analysed for macroscopic and microscopic neoplasms. Results-Plasma and colonic folate concentrations correlated directly with dietary fol ate levels (p<0 . 005). The incidence of microscopic neoplasms was sim ilar among the four groups. However, the incidence and the average num ber of macroscopic tumours per rat decreased progressively with increa sing dietary folate levels up to 8 mg/kg diet (p<0 . 05). In the stron gly procarcinogenic milieu used in this study, folate supplementation at 20 times the basal requirement was associated with rates of macrosc opic tumour development that were intermediate, and not statistically distinct, from rates observed at either 0 or 8 mg/kg diet. Conclusions -These data indicate that in this rat model, (a) increasing dietary fo late up to four times the basal requirement leads to a progressive red uction in the evolution of macroscopic neoplasms from microscopic foci ; and (b) folate supplementation beyond four times the requirement doe s not convey further benefit.