Initiation by nickel acetate and promotion by sodium barbital of renal cortical epithelial tumors in male F344 rats

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Abstract
Soluble nickel(II) ion, given to male F344/NCr rats as a single i.p. injection of nickel(II) acetate tetrahydrate at a dose of 90 μmol/kg body weight at 5 weeks of age, proved an effective initiator of renal cortical epithelial tumors. The tumors were revealed by subsequent dosing with the known renal tumor promoter, sodium barbital (5,5-diethylbarbituric acid, sodium salt) dissolved in drinking water at a concentration of 500 p.p.m. Only one rat given the nickel injection without subsequent promotion developed a single renal cortical adenoma, while multiple tumors were common in nickel(II) initiated/sodium barbital promoted rats. Renal cortical adenocarcinomas, some of them metastatic to lung, liver, and spleen, occurred only in initiated/promoted rats. No excess incidence of nickel-initiated tumors was found in any other tissues in which sodium barbital is known to promote carcinogenesis, such as liver or thyroid. A single i.p. injection of the Ni (II) salt, 95 μmol/kg, appeared to be associated with an increased concentration of 8-hydroxy-2'-deoxyguanosine in DNA extracted from kidneys of rats 16–48 h after injection.