DHA feeding provides host protection and prevents fibrosarcoma‐induced hyperlipidemia while maintaining the tumor response to araC in Fischer 344 rats

Abstract

Fischer 344 rats were inoculated with fibrosarcoma tumor cells and fed diets containing 5% or 10% (wt/wt) safflower oil or 10% oil containing docosahexaenoic acid (DHA). Animals were then treated with arabinosylcytosine (araC) or saline for six days. Tumor weights were highest in animals fed 10% safflower oil and treated with saline, intermediate in animals fed oil containing DHA and 5% safflower oil and treated with saline, and lowest in araC-treated animals from all diets. Plasma cholesterol and triglyceride levels correlated highly with final tumor size, regardless of diet or treatment group. Animals fed safflower oil had lower intestinal weights than those fed DHA, which histology demonstrated to be a result of differences in villus height and crypt depth. Substantial loss of bone marrow cells occurred in all dietary groups treated with araC; however, the proportion of granulocyte-macrophage precursors remaining in the DHA animals was higher than in saline-treated animals and twofold higher than in the animals fed 10% safflower oil and treated with araC. These data suggest that, even in the face of rapid tumor growth and chemotherapeutic challenge, consumption of a diet rich in DHA can slow tumor growth, prevent hyperlipidemia, enhance bone marrow cellularity, and promote intestinal growth compared with a moderate-fat n--6-rich diet.

Tumor and non-tumor tissues differential oxidative stress response to supplemental DHA and chemotherapy in rats

“…The high level of DHA in liver and heart (11.5 %) in unsupplemented rats was likely due to a signiWcant endogenous synthesis of DHA from its precursor alpha-linolenic acid in these tissues [38]. These results are concordant with the previous studies [19,20]. Enrichment of normal cells or tissues with DHA or EPA alone (without chemotherapy) did not increase their susceptibility to oxidative stress [39][40][41].…”

“…Despite the ubiquitous distribution of DHA, EPA [18][19][20], and chemotherapy to tissues, no additional toxicity to non-tumor tissues has been reported experimentally [6-9, 13, 21-25] or in patients [16,17]. This lack of toxicity to non-tumor tissues is not well understood.…”

DHA Effect on Chemotherapy-Induced Body Weight Loss: An Exploratory Study in a Rodent Model of Mammary Tumors

“…Only a few studies have investigated the effect of DHA alone on body weight during chemotherapy. One study in healthy mice showed that DHA reduced body weight loss related to treatment with methotrexate (34), whereas 2 other studies showed an effect on body weight loss related to cytarabine neither in healthy rats (35) nor in rats bearing fibrosarcoma (36). In the present study, a diet enriched with DHA prevented body weight loss related to doxorubicin in rats bearing mammary tumors.…”

The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy

“…In vitro, DHA and/or EPA improve cytotoxic effects of several anticancer drugs [doxorubicin, epirubicin, paclitaxel, 5-fluorouracil, cytosine arabinoside (Ara-C), mitomycin, arsenic trioxide] toward various human cancer cell lines, including those of breast, colon, bladder, neuroblastoma, and glioblastoma [5][6][7][8][9][10][11][12][13]. In animal models, representing a variety of tumor sites, dietary supplementation with DHA and/or EPA in combination with chemotherapeutic drugs (Ara-C, doxorubicin, epirubicin, irinotecan, methotrexate) decreased tumor size [14][15][16], reduced side effects [17][18][19][20] and prolonged survival [21,22] (Table 1).…”