Dietary docosahexaenoic acid levels influence the outcome of arabinosylcytosine chemotherapy in L1210 leukemic mice.
The purpose of this study was to investigate whether dietary supplementation with the n-3 fatty acid docosahexaenoic acid (DHA) in combination with arabinosylcytosine (AraC) chemotherapy could prolong the life expectancy of mice bearing L1210 leukemia. The four control diets included rodent chow, a diet containing 5% of a blended oil mimicking the fatty acid composition of rodent chow, and diets containing 5% or 10% fat with safflower oil as the main oil source. The two DHA-supplemented diets provided 1.5% or 3.5% DHA and 5% or 10% total fat, respectively. After tumor cell inoculation, mice were treated with AraC for 10 days. Mice fed the 5% safflower oil diet (30.1 -/+ 4.1 days), but not those fed the 10% safflower oil diet, survived longer than the chow-fed animals (22.1 -/+ 3.1 days, P = 0.05). The 1.5%-/+ DHA diet (average intake 1.8 g DHA/kg/day) was associated with a longer life span (33.3 -/+ 3.4 days, P < 0.01 vs. chow-fed) and no incidence of death due to drug toxicity. Further increasing DHA intake (4.5 g DHA/kg/day) resulted in shortened survival time (26.5 -/+ 2.0 days), increased circulating tumor cell burden, and lowered red blood cell concentrations. These data suggest that a modest level of dietary DHA or linoleic acid supplementation may improve the antineoplastic efficacy of AraC. However, overconsumption of DHA reverses the beneficial effect of DHA intake on drug sensitivity.
Cha
Ming C
MC
Department of Human Biology and Nutrition Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1.
Meckling
Kelly A
KA
Stewart
Christine
C
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000627:therapeutic use*; D003561:Cytarabine / Q000097:blood / Q000627:therapeutic use*; D019587:Dietary Supplements / Q000706:statistics & numerical data*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004906:Erythrocyte Count / Q000706:statistics & numerical data; D007939:Leukemia L1210 / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D007958:Leukocyte Count / Q000706:statistics & numerical data; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010976:Platelet Count / Q000706:statistics & numerical data; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D004281:Docosahexaenoic Acids