Effects of essential divalent metals on carcinogenicity and metabolism of nickel and cadmium |
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Authors: | Kazimierz S Kasprzak Michael P Waalkes Lionel A Poirier |
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Affiliation: | (1) Nutrition and Metabolism Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRF, 21701 Frederick, MD, USA |
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Abstract: | Interactions between the physiologically essential metals calcium, magnesium, and zinc and the carcinogenic metals nickel
and cadmium were investigated to help elucidate the mechanisms of action of the carcinogenic metals. Bioassay studies revealed
several significant findings, including: (1) the ability of magnesium and calcium to inhibit nickel-induced elevation of pulmonary
adenoma incidence in strain A mice; (2) the ability of magnesium, but not of calcium, to prevent cadmium-induced subcutaneous
sarcoma formation; and (3) the ability of magnesium, but not of calcium, to inhibit nickel-induced muscle tumor formation.
Biochemical studies indicated a direct relationship between the antitumorigenic potential of magnesium and the capacity of
this metal to: (1) inhibit nickel and cadmium uptake by the target tissues in vivo; (2) inhibit nickel-induced disturbances
in DNA synthesis in vivo; (3) inhibit nuclear and cytosolic uptake of nickel by the target tissue cells in vivo; and (4) inhibit
nickel and cadmium binding to DNA in vitro. Calcium, which in most cases did not prevent carcinogenesis, had no consistent
influence on the uptake of carcinogenic metals or their biochemical effects in the target tissues. Magnesium and zinc, but
not calcium, were also found to attenuate the acute toxic effects of nickel, indicating a possible correlation between prevention
of acute effects and reduction in tumorigenicity. Zinc, which antagonizes cadmium tumorigenicity in the rat testis, was found
to reduce markedly cadmium uptake into isolated testicular interstitial cells. Also, zinc was found to inhibit strongly cadmium
binding to DNA in vitro. |
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Keywords: | Carcinogenesis metal carcinogenicity metal toxicity metal interactions nickel cadmium calcium magnesium zinc |
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