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Iron Deficiency Alters DMBA-Induced Tumor Burden and Natural Killer Cell Cytotoxicity in Rats¹

Department of Nutritional Sciences, Cook College, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903

Natural killer (NK) cell activity is impaired in iron-deficient rats. Natural killer cells destroy tumor cells; therefore, iron-deficient rats may be less able to combat cancer growth. Natural killer cell cytotoxicity, both basal and interferon gamma (IFN )-stimulated, was studied in moderately and severely iron-deficient rats challenged with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Female weanling rats were fed ad libitum semipurified diets containing 8, 13 or 42 mg Fe/kg. A pair-fed group was fed the 42 mg Fe/kg diet at the level consumed by the 8 mg Fe/kg group. Following 6 wk of dietary treatment, DMBA-treated rats received a single intragastric dose of DMBA. Dietary treatment was continued. Rats were killed at 1, 4, 8, 14 and 20 wk post-DMBA treatment. Natural killer cell cytotoxicity (both basal and IFN -stimulated) was analyzed. Feeding the 13 mg Fe/kg diet resulted in lower NK cell activity (P = 0.006) and greater tumor burden (P = 0.045) and tumor incidence. Interferon gamma treatment relieved the lower NK cell cytotoxicity observed in moderate iron deficiency. Feeding the 8 mg Fe/kg diet impaired NK cell activity (P = 0.006), but tumor burden and incidence were less than in moderate iron deficiency. In this model, iron deficiency, particularly moderate iron deficiency, contributed to cancer development and compromised NK cell cytotoxicity.

KEY WORDS: • iron deficiency • cancer • rats • natural killer cell • interferon

¹ Supported in part by a grant from Elsa U. Pardee Foundation and by the New Jersey Agricultural Experiment Station. This is New Jersey Agricultural Experiment Station Publication number D-14150-1-91.

Manuscript received 10 April 1991. Revision accepted 13 June 1991.