Comparative effects of disulfiram and diethyldithiocarbamate on cadmium distribution in mice.
It has been reported that disulfiram (DSF) and diethyldithiocarbamate (DDTC) have similar actions on cadmium (Cd) distribution in maternal and fetal organs when given to pregnant mice prior to and again immediately after iv administration of Cd (Arch. Toxicol. 55, 161-167, 1984). We have now examined Cd distribution in mice in which virtually all of the Cd was bound to metallothionein (MT) in an attempt to simulate more closely the condition of low level, chronic Cd exposure. When DSF was incorporated into food and ingested by mice over a 4-hr period on each of four days, hepatic and pulmonary Cd levels were reduced significantly. When given ip at 500 mg/kg, DDTC lowered hepatic, renal, splenic, and pancreatic Cd levels, but increased Cd concentrations in brain, testes, heart, and lungs. When DSF was given at 500 mg/kg ip, it lowered hepatic, splenic, testicular, and pancreatic Cd levels, but increased Cd concentrations in heart and brain. In contrast to DDTC, DSF had no effect on pulmonary or renal Cd. When given as a bolus dose po for five days at 1.0 mmole/kg, DDTC lowered renal, splenic, testicular, and pancreatic Cd levels, but increased Cd concentrations in brain and heart. There was no effect on hepatic or pulmonary Cd. When given at the same dose po, DSF did not alter the Cd concentration of any organ assessed. We suggest that studies of interactions of various xenobiotics with Cd in vivo should be done with an animal model which simulates chronic Cd exposure rather than acute Cd intoxication.
Gale
G R
GR
Veterans Administration Medical Center, Charleston, SC 29403.
Smith
A B
AB
Atkins
L M
LM
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D002106:Cadmium Radioisotopes; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D014018:Tissue Distribution
D002106:Cadmium Radioisotopes; D002104:Cadmium; D004050:Ditiocarb; D004221:Disulfiram