Transplacental passage and fetal kidney binding of 14C-dichlorovinyl cysteine (DCVC) in mice.
In order to assess the potential hazard of the nephrotoxic compound S-1,2-dichlorovinyl-L-cysteine (DCVC) during gestation, studies on its disposition and degenerative effects were performed in pregnant mice. In late gestation, binding of 14C-DCVC (spec. act. 1.01 microCi/mumol) equivalents was observed by autoradiography in the inner cortex of the kidney, in the liver and gastrointestinal tract of the fetuses. The uptake of radioactivity in the fetal kidney increased from day 13 to day 18 of gestation when measured by liquid scintillation. When fetuses were injected in utero, a distinct binding of 14C-DCVC was present in the kidney cortex. This fact suggests that bioactivation occurs in situ, as the reactive products are not likely to be transported far from their site of formation. The concentration of radioactivity in the fetal kidney at day 18 of gestation was about 10% of that found in the maternal kidney. Limiting factors for fetal kidney uptake may be both transplacental transfer, and renal bioactivation and transport activities. No distinct histopathological changes in the fetal kidney were observed when a nephrotoxic dose (25 mg/kg) of DCVC was given to the dam. These results suggest that the fetal kidney during late gestation is able to activate and bind DCVC. However, the degree of fetal binding seems too low to cause any visible histopathological effects.
Darnerud
P O
PO
Department of Toxicology, Uppsala University, Sweden.
Olsson
L
L
D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012588:Scintillation Counting / Q000379:methods
D002250:Carbon Radioisotopes; C039961:S-(1,2-dichlorovinyl)cysteine; D003545:Cysteine