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Interactions of Trace Metals in Rat Tissues. Cadmium and Nickel with Zinc, Chromium, Copper, Manganese^1,2,

Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755 and Brattleboro Memorial Hospital, Brattleboro, Vermont 05301

In order to ascertain what effect one essential trace metal might have on tissue concentrations of another, rats of the Long-Evans strain were born and raised in an environment controlled as to contaminating trace metals until natural death, and fed a diet of rye flour, dry skim milk and corn oil. One group of 60 was given plain deionized water for a year and then killed. Two groups of 100 or more equally divided as to sex were given a basal water containing added zinc (50 ppm), manganese (10 ppm), chromium (5 ppm), copper (5 ppm), cobalt (1 ppm) and molybdenum (1 ppm) as soluble salts, or this basal water without chromium. Two other groups were given cadmium (50 ppm) or nickel (5 ppm) in the chromium-containing basal water. Five organs from each rat were ashed and analyzed for zinc, copper, manganese, chromium and cadmium by atomic absorption spectrophotometry. Compared with the group given plain water, zinc was markedly increased in all organs of rats given the basal water, copper was increased in liver, lung and spleen, and chromium was increased in liver and lung. In the group given nickel and the basal water, zinc was increased in all organs but liver, copper was increased in spleen, manganese was increased in lung and kidney, and chromium was increased in liver and kidney, compared to the plain water group. Chromium was especially concentrated in spleen and heart, copper in heart and kidney and manganese in liver of rats given plain water. When rats were given basal water plus cadmium (50 ppm), there was a marked increase in zinc in all organs but spleen, and a very marked increase in cadmium in all organs from very low levels (0.03 ppm, wet weight when no cadmium was given). Consumption of basal water plus cadmium was also associated with some depression of heart chromium, an increase in kidney and liver manganese levels and an increase in renal copper. From observations on the effect of increasing the intake of trace metals via water on the tissue levels of the respective trace metals, the following conclusions are suggested: a) that zinc at a level of 22 µg/g diet and copper at 1.4 µg/g diet were adequate for growth but inadequate for filling all binding sites and stores, b) that manganese at 13 µg/g diet may be insufficient for repletion of splenic manganese stores, c) that chromium at 0.14 µg/g diet produces partial chromium deficiency, and d) that cadmium at 0.07 µg/g diet does not cause cadmium accumulation with age and is thus in balance. The data also demonstrate interactions of cadmium with zinc, manganese and copper, and interactions of nickel with copper and manganese in some organs.

KEY WORDS: • mineral metabolism • trace minerals • metallic micronutrients

¹ See NAPS document #02277 for 15 pages of supplementary material. Order from ASIS/NAPS, c/o Microfiche Publications, 305 E. 46th St., New York, N. Y. 10017. Remit in advance for each NAPS accession number $1.50 for microfiche or $5.00 for photocopies. Make checks payable to Microfiche Publications.

² Supported by Public Health Service Research Grant ES 00699-13A1, Ciba-Geigy Corporation and Cooper Laboratories, Inc.

³ Present address: 9 Belmont Avenue, Brattleboro, Vt. 05301.

Manuscript received 6 November 1972.