Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1 mice.
Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 ppm or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 ppm or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33-35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal.
Inorganic Toxicology Group, National Toxicology Program Laboratory Branch, Division of the National Toxicology Program, the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Erik J
EJ
Tokar
Bhalchandra A
BA
Diwan
Michael P
MP
Waalkes
D000310:Adrenal Gland Neoplasms / Q000139:chemically induced*; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002101:Cacodylic Acid / Q000633:toxicity*; D005260:Female; D006651:Histocytochemistry; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008113:Liver Neoplasms / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D016019:Survival Analysis
D002101:Cacodylic Acid; D001151:Arsenic