Dietary polyunsatured fatty acids (PUFA) differentially modulate melamine-induced preneoplastic urothelial proliferation and apoptosis in mice

A number of experimental and epidemiological studies indicate that dietary polyunsaturated fatty acids (PUFA) play a modulatory role in the development of several cancers. However, literature on the importance of dietary PUFA in urinary-tract tumourigenesis is scarce, and even contradictory. Therefore, our purpose was to evaluate comparatively, several urothelial cellular parameters linked to neoplasia when 180 BALB/c mice were initiated with the tumourigenic agent melamine and fed with two amounts of different PUFA. In experiment 1, mice were fed with 6% of fish oil (enriched in n-3 PUFA, FO), corn oil (enriched in n-6, CO) and olein (enriched in n-9, an EFA deficiency inducer) formulae plus two chow-fed control lots with (CM) and without (C) melamine treatment. In experiment 2, each of the three varieties of PUFA were offered at 10%. Following 18-22 weeks of melamine treatment, animals were autopsied. The liver fatty acid profile showed a close correlation with the dietary sources, exhibiting in the O group macroscopic and biochemical EFA-deficient (EFAD) characteristics. The frequency of simple urothelial hyperplasias (H) and dysplasia/carcinoma in situ (D/CIS) was significantly lower in the FO group, whereas both types of lesions increased in the CO and O groups, compared to the C and CM mice. Increased proliferation and abnormal luminal localized mitosis were more frequently recorded in EFAD mice, whereas abnormal apoptotic/mitosis ratio increased in both olein- and corn-oil-fed animals. This study shows that dietary PUFA modulate differentially normal and pre-neoplastic proliferation when induced by the tumorigenic agent melamine. Fish oil, rich in n-3 fatty acids, exhibits a clear antipromoting activity, whereas the role of n-6 and n-9 PUFA derivatives needs further research.