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

Abstract

We wanted to examine the effects of an oil rich in docosahexaenoic acid (DHA), without eicosapentaenoic acid, on the composition of membrane phospholipid in a variety of tissues. Our in vitro studies had previously shown that DHA could modify glucose and nucleoside transport in cells in culture and also increase selectivity of the nucleoside drug, arabinosylcytosine (araC) toward tumor cells. Here we wanted to examine what effect DHA supplementation would have in the whole animal in terms of the chemosensitivity of normal bone marrow, the dose-limiting tissue during chemotherapy, to araC. The purpose was to determine whether fatty acid supplementation might be useful as an adjuvant to chemotherapy. We fed diets containing 5% (w/w) low fat-corn oil (LF-CO group), 10% moderate fat-safflower oil (MF-SO group), or 10% DHASCO^TM (MF-DHA group) to weanling Fischer 344 rats for 8–9 wk. Feed intake and growth were not different between the different diets. Similarly, treatment of animals with the chemotherapeutic drug araC did not differentially affect growth, feed intake, or tissue fatty acid composition for the different diet groups. Fatty acid compositions of bone marrow, liver, red blood cells, plasma phospholipid and triglyceride, as well as skeletal and cardiac muscle, were substantially different between the dietary groups. The DHASCO^TM oil contained 46% DHA (22:6n-3) and resulted in profound incorporation of DHA in all tissues examined. The most dramatic response was seen in skeletal muscle of MF-DHA fed animals where DHA represented 46% of membrane phospholipid fatty acids. This is likely to have consequences to muscle function. Although DHASCO^TM contains a similar level of saturated fatty acids (42%), few differences in saturates were noted between the various dietary groups for most of the tissues examined. Both LF-CO and MF-SO diets were hypercholesterolemic, and the LF-CO was also hypertriglyceridemic compared to the chow-fed animals. Animals fed the MF-DHA diet had the lowest triglyceride levels of any of the treatment groups and cholesterol levels comparable to chow-fed animals. MF-DHA had substantially higher numbers of colony-forming units-granulocyte macrophage (CFU-GM) as reflected in a twofold 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 MF group. Thus, DHA, fed as DHASCO^TM, has advantages over low or moderate 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.