EFFECT OF FISH-OIL ON CANCER CACHEXIA AND HOST LIVER-METABOLISM IN RATS WITH PROSTATE TUMORS

The aim of this study was to investigate whether tumor-induced cachexi a and aberrations in host liver metabolism, induced by the MAT-LyLu va riant of the Dunning prostate tumor, could be prevented by omega 3 fat ty acids hom fish oil. On day 0, adult Copenhagen-Fisher rats fed norm al chow ad libitum were inoculated with 10(6) MAT-LyLu cells (n = 14) or saline (n = 9). On day 7, when tumors were palpable, four tumor-bea ring (TB) and four nontumorbearing (NTB) rats were put on isocaloric d iets with 50% of total energy as fish oil. The introduction of fish oi l-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7-14 (di fference by dietary group: NTB, P < 0.001; TB, P < 0.001). During days 14-21, energy intake in fish oil-fed animals returned to approximatel y 75% of energy intake by animals fed normal diets (difference by diet ary group: NTB, P < 0.003; TB, P = 0.001). Carcass weight of animals o n day 21, when the study was terminated, was significantly related to initial weight (P = 0.05) and mean food intake during the study (P = 0 .01). When data were adjusted for these variables using analysis of co variance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on norma l diets only (mean +/- SEM 58 +/- 10 g loss, P < 0.001), but not in TB animals on fish oil diets (8 +/- 18 g loss, P = 0.67). This positive effect of fish oil diets on carcass weight in TB animals was statistic ally significant (50 +/- 19 g, P < 0.02), implicating that the fish oi l enriched diet inhibited tumor-induced weight loss by more than 85%. No effect of fish oil diets on tumor growth was detected. In all TB an imals, regardless of diet, hepatic [P-i]/[adenosine triphosphate] rati os measured by P-31 magnetic resonance spectroscopy (MRS) in vivo and in vitro were elevated, and absolute concentrations of phosphocholine, glycerophosphocho-line, glycerophosphoethanolamine and glucose-6-phos phate as determined by P-31 MRS in vitro were reduced. Ultrastructural studies of Liver tissue revealed increased numbers of mitochondria an d increased amounts of endoplasmic reticulum in the host liver of TB a nimals, without differences between dietary group. In conclusion, fish oil supplementation partially inhibited MAT-LyLu tumor-induced cachex ia, but did not prevent the majority of (31)p MRS detectable alteratio ns in host liver metabolism.