Effect of 6-mercaptopurine on 65Zn distribution in the pregnant rat.
The effect of 6-mercaptopurine (6-MP) on the distribution of gavaged 65Zn in maternal and embryonic tissues of Sprague-Dawley rats was examined 24 hr after injection of the drug on day 13 of pregnancy. 6-MP injection resulted in a significantly higher retention of counts of 65Zn in maternal liver and lower counts in maternal plasma, uterus, placenta, and embryo than in controls. Compared to controls, gel chromatography of maternal liver from 6-MP injected dams showed higher counts associated with a protein peak of molecular weight 6,000-8,000, the approximate molecular weight of the zinc-binding protein metallothionein. These results support the idea that the zinc deficiency, which is observed in day 21 fetuses from dams injected with 6-MP during midgestation, may be the result of a drug-induced sequestering of zinc into maternal liver followed by a decrease in maternal plasma zinc and subsequent reduction in fetal zinc uptake. We suggest that this 6-MP-associated redistribution of zinc into maternal liver may be due to induction of maternal metallothionein synthesis by the drug.
Amemiya
K
K
Department of Nutrition, University of California, Davis 95616.
Hurley
L S
LS
Keen
C L
CL
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000378:metabolism; D002850:Chromatography, Gel; D003300:Copper / Q000493:pharmacokinetics; D004435:Eating / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D015122:Mercaptopurine / Q000633:toxicity*; D008668:Metallothionein / Q000096:biosynthesis; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens; D015032:Zinc / Q000172:deficiency / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015037:Zinc Radioisotopes
D002352:Carrier Proteins; D013723:Teratogens; D015037:Zinc Radioisotopes; C017800:zinc-binding protein; D003300:Copper; D008668:Metallothionein; D015122:Mercaptopurine; D015032:Zinc; D002118:Calcium