INCORPORATION OF LONG-CHAIN N-3 FATTY-ACIDS IN TISSUES AND ENHANCED BONE-MARROW CELLULARITY WITH DOCOSAHEXAENOIC ACID FEEDING IN POST-WEANLING FISCHER-344 RATS

We wanted to examine the effects of an oil rich in docosahexaenoic aci d (DHA), without eicosapentaenoic acid, on the composition of membrane phospholipid in a variety of tissues, Our in vitro studies had previo usly shown that DHA could modify glucose and nucleoside transport in c ells in culture and also increase selectivity of the nucleoside drug, arabinosylcytosine (araC) toward tumor cells. Here we wanted to examin e what effect DHA supplementation would have in the whole animal in te rms of the chemosensitivity of normal bone marrow, the dose-limiting t issue during chemotherapy, to araC. The purpose was to determine wheth er fatty acid supplementation might be useful as an adjuvant to chemot herapy. We fed diets containing 5% (w/w) low fat-corn oil (LF-CO group ), 10% moderate fat-safflower oil (MF-SO group), or 10% DHASCOTM (MF-D HA group) to weanling Fischer 344 rats for 8-9 wk, Feed intake and gro wth were not different between the different diets. Similarly, treatme nt of animals with the chemotherapeutic drug araC did not differential ly affect growth, feed intake, or tissue fatty acid composition for th e different diet groups. Fatty acid compositions of bone marrow, liver , red blood cells, plasma phospholipid and triglyceride, as well as sk eletal and cardiac muscle, were substantially different between the di etary groups, The DHASCOTM oil contained 46% DHA (22:6n-3) and resulte d in profound incorporation of DHA in all tissues examined. The most d ramatic response was seen in skeletal muscle of MF-DHA fed animals whe re DHA represented 46% of membrane phospholipid fatty acids. This is l ikely to have consequences to muscle function. Although DHASCOTM conta ins a similar level of saturated fatty acids (42%), few differences in saturates were noted between the various dietary groups for most of t he tissues examined. Both LF-CO and MF-SO diets were hypercholesterole mic, and the LF-CO was also hypertriglyceridemic compared to the chow- fed animals. Animals fed the MF-DHA diet had the lowest triglyceride l evels of any of the treatment groups and cholesterol levels comparable to chow-fed animals. MF-DHA had substantially higher numbers of colon y-forming units-granulocyte macrophage (CFU-GM) as reflected in a twof old higher bone marrow cellularity than either chow or LF-CO animals, suggesting expansion of the bone marrow compartment with DHA feeding, Although higher than LF-SO, the number of CFU-GM in MF-SO animals was not significantly higher than animals fed chow. Bone marrow from LF-CO animals appeared to be more resistant to araC treatment than either M F group. Thus, DHA, fed as DHASCOTM, has advantages over low or modera te n-6 diets and chow as it is has both hypolipidemic- and bone marrow -enhancing properties in weanling Fischer 344 rats, This suggests that DHA supplementation may be useful in adjuvant chemotherapy.