Transplacental carcinogenic effects of nickel(II) acetate in the renal cortex, renal pelvis and adenohypophysis in F344/NCr rats.
Nickel(II) acetate (NiAcet), a soluble nickel salt known to be an effective initiator of renal epithelial tumors in adult rats, was studied for possible transplacental carcinogenicity. Pregnant F344/NCr rats were given NiAcet i.p. either once a day on day 17 (90 mumol/kg body wt; group 1) or twice on days 16 and 18 of gestation (45 mumol/kg body wt/day; group 2). Offspring of these rats were further subdivided into groups 1A and B and 2A and B, respectively. Groups 1A and 2A received ordinary tap water while groups 1B and 2B received drinking water containing 500 p.p.m. sodium barbital (NaBB) during weeks 4-85 of age. Renal cortical epithelial and renal pelvic transitional epithelial tumors occurred in male offspring given NiAcet prenatally followed by NaBB postnatally (group 1B, 15 tumors in 8/15 rats; group 2B, 10 tumors in 7/15), but not in male offspring given NiAcet only (0/32) or in controls given prenatal sodium acetate (NaAcet) only (0/15) and rarely in males given NaAcet followed by the promoter NaBB (1/15). No renal tumors occurred in females. Pituitary tumor incidence was significantly higher in offspring of both sexes given NiAcet prenatally (NaAcet controls, 4/31, both sexes combined; group 1A, 14/33, P = 0.012; group 2A, 14/31, P = 0.008). Pituitary tumors appeared much earlier in rats given NiAcet prenatally, with or without postnatal NaBB, and often were malignant by cytologic and histologic criteria including pleomorphism and invasion of adjacent structures, unlike the well-differentiated adenomas that occurred less frequently in untreated rats. These results are the first evidence that Ni(II) is a potent transplacental initiator of epithelial tumors in fetal rat kidney and a complete transplacental carcinogen for rat pituitary.
Diwan
B A
BA
Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.
Kasprzak
K S
KS
Rice
J M
JM
D000085:Acetates / Q000009:adverse effects*; D019342:Acetic Acid; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D001463:Barbiturates / Q000009:adverse effects; D001835:Body Weight; D002277:Carcinoma / Q000139:chemically induced; D005260:Female; D007672:Kidney Cortex / Q000187:drug effects* / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000401:mortality; D007682:Kidney Pelvis / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange; D010212:Papilloma / Q000139:chemically induced; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000139:chemically induced*; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D000085:Acetates; D001463:Barbiturates; D019342:Acetic Acid; C032232:barbituric acid