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.
Cremonezzi
D C
DC
Facultad de Ciencias Médicas, Instituto de Biología Celular, Universidad Nacional de Córdoba, Córdoba, República Argentina.
Silva
R A
RA
del Pilar Díaz
M
M
Valentich
M A
MA
Eynard
A R
AR
D000818:Animals; D017209:Apoptosis; D002278:Carcinoma in Situ / Q000378:metabolism; D002455:Cell Division; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006965:Hyperplasia / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis; D011230:Precancerous Conditions / Q000378:metabolism*; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*; D014513:Ureter / Q000473:pathology; D001743:Urinary Bladder / Q000473:pathology; D014571:Urologic Neoplasms / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000166:cytology* / Q000473:pathology*
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D014227:Triazines; C011907:melamine