Inhibitory effect of zinc on nickel subsulfide carcinogenesis in Fischer rats.
The effects of zinc oxide (ZnO) and zinc acetate (ZnAcet) administered i.m. together with nickel subsulfide (Ni3S2), a potent muscle carcinogen, were observed over 66 weeks in male F344/NCr rats. The rats (20/group) received a single injection of 2.5 mg Ni3S2 (equal to 31 mumol Ni) alone or combined with different molar proportions of ZnO or ZnAcet (8-60 mumol Zn) into both thighs. One more group of rats given i.m. Ni3S2 received s.c. ZnO (60 mumol Zn) at the nape of the neck. Control rats were treated with i.m. ZnO (60 mumol Zn) or the injection vehicle, water. In rats given Ni3S2 alone the incidence of local tumors reached 100% in 40 weeks. In rats treated locally with Ni3S2 + ZnO or ZnAcet, the tumor incidence at week 40 was only 40-60%; it reached 85-100% in 66 weeks, with no significant differences among the treatments. Treatment with i.m. Ni3S2 + s.c. ZnO resulted in 100% muscle tumors at week 58. One local tumor was found in rats given ZnO alone and none in the water injected animals. Statistical analysis revealed highly significant differences in the tumor occurrence rates between rats treated with Ni3S2 alone and rats treated with Ni3S2 combined with ZnO or ZnAcet, whereas the final tumor incidences at week 66 were not different. The first tumors were found at weeks 24-31 regardless of the treatment. Hence, administration of zinc slows the carcinogenic process induced by nickel. This effect has a systemic character and is produced by both water-soluble and insoluble zinc compounds despite their different retention times in the muscle. The half-lives of ZnO and ZnAcet in the muscle were approx. 24 days and 2.5 days, respectively; that of Ni3S2 was 21 days. Zinc in either form exerted no apparent influence upon the retention of nickel at the injection site and did not significantly affect the early local cellular reactions to nickel.
Kasprzak
K S
KS
Division of Cancer Etiology, National Cancer Institute, FCRF, Frederick, MD 21701.
Kovatch
R M
RM
Poirier
L A
LA
D000085:Acetates / Q000494:pharmacology*; D019342:Acetic Acid; D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D008297:Male; D009135:Muscular Diseases / Q000139:chemically induced / Q000517:prevention & control*; D009532:Nickel / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000517:prevention & control; D015032:Zinc / Q000494:pharmacology*; D015034:Zinc Oxide / Q000494:pharmacology*
D000085:Acetates; D002273:Carcinogens; D009532:Nickel; D015032:Zinc; D019342:Acetic Acid; D015034:Zinc Oxide; C017557:nickel subsulfide