Initiation by nickel acetate and promotion by sodium barbital of renal cortical epithelial tumors in male F344 rats.
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 mumols/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 mumols/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.
Kasprzak
K S
KS
Laboratory of Comparative Carcinogenesis, National Cancer Institute, MD 21701.
Diwan
B A
BA
Konishi
N
N
Misra
M
M
Rice
J M
JM
D000085:Acetates / Q000633:toxicity*; D019342:Acetic Acid; D000818:Animals; D001463:Barbiturates / Q000633:toxicity*; D001835:Body Weight; D002273:Carcinogens; D004848:Epithelium / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects* / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344
D000085:Acetates; D001463:Barbiturates; D002273:Carcinogens; D019342:Acetic Acid; C032232:barbituric acid