Iron repletion attenuates the protective effects of iron deficiency in DMBA-induced mammary tumors in rats.
Mammary tumor incidence, natural killer (NK) cell activity, and tumor necrosis factor-alpha (TNF-alpha) activity were measured in iron (Fe)-deficient and iron-replete rats treated with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Female weanling rats were fed AIN-76 diets: the iron-deficient group was fed 5 mg Fe/kg diet; the control group was fed 50 mg Fe/kg diet; the food-restricted group was fed 50 mg Fe/kg diet in the amount consumed by the iron-deficient group; and the replete group was fed 5 mg Fe/kg diet for 45 days and then 50 mg Fe/kg diet. After six weeks of feeding, the rats were given a single intragastric dose of DMBA. Feeding the iron-deficient diet for 20 weeks reduced hematocrit, hemoglobin, liver iron, and tumor iron values and increased spleen weight. Dietary iron repletion for 14 weeks reversed these effects of iron deficiency. Splenic NK cell cytotoxicity against YAC-1 cells was highest in the control group. Repleting rats with 50 mg Fe/kg diet corrected iron deficiency but did not restore NK cell cytotoxicity. No significant differences in macrophage TNF-alpha bioactivity were found among groups. Cumulative tumor incidence over all weeks was lowest in the iron-deficient rats. Iron repletion during the promotion phase of tumorigenesis attenuates the protective effects of iron deficiency. Food restriction to the extent present in the iron-deficient group did not protect against tumorigenesis. The iron-deficient group had the lowest tumor burden and delayed onset of tumors. Iron deficiency significantly reduces tumor incidence in DMBA-treated rats by mechanisms other than NK cell cytotoxicity, TNF-alpha activity, and food restriction.
Hrabinski
D
D
Department of Nutritional Sciences, Rutgers, State University of New Jersey, New Brunswick 08903, USA.
Hertz
J L
JL
Tantillo
C
C
Berger
V
V
Sherman
A R
AR
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001835:Body Weight; D002273:Carcinogens; D004435:Eating; D005260:Female; D007501:Iron / Q000494:pharmacology*; D000090463:Iron Deficiencies; D007694:Killer Cells, Natural / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D002273:Carcinogens; D014409:Tumor Necrosis Factor-alpha; D015127:9,10-Dimethyl-1,2-benzanthracene; D007501:Iron