Neoplastic and preneoplastic lesions induced by melamine in rat urothelium are modulated by dietary polyunsaturated fatty acids

The modulatory effects of polyunsaturated fatty acids (PUFA) on urinary tract tumorigenesis of 275 Wistar rats were evaluated by treating animals with the tumorigenic agent melamine. Rats were fed with formulae containing 6% of 4 varieties of fats: fish oil enriched in n-3 PUFA (FO), corn oil enriched in n-6 (CO), olein containing mainly n-9 oleic acid (O), and 98% stearic acid (SA), the latter two being essential (EFA)-deficient inducers. Two commercially fed control groups with (CM) and without (C) melamine were used. Animals were autopsied at 22–25 and at 36–40 weeks. Hepatic fatty acids showed that O and SA groups were EFA-deficient. Simple well differentiated hyperplasias were significantly higher in the FO lot, whereas dysplasia was increased in the CO, O and SA lots. Most of the animals fed for 36–40 weeks with the three latter formulae developed the more severe lesions. Increased urothelial proliferation was more frequent in EFA-deficient rats. The apoptosis/mitosis ratio was higher in O, SA and CO fed animals with respect to FO and chow ones. Results show that dietary PUFA modulate differentially both normal and pre-neoplastic urothelial proliferation induced by melamine. FO, rich in n-3 fatty acids, showed a strong protective effect.