S-(1,2-dichloro-[14C]vinyl)-L-cysteine (DCVC) in the mouse kidney: correlation between tissue-binding and toxicity.
Uniformly 14C-labeled DCVC and unlabeled DCVC were synthesized and used for autoradiographical and histopathological studies. Four hours after administration of [14C]DCVC (25 mg/kg body wt), a strong binding of radioactivity was observed in the straight proximal tubular cells. Later, the radioactivity was redistributed from the proximal tubules to scattered foci in the kidney medulla, suggesting desquamation and tubular transport of labeled epithelial cells. The redistribution was less pronounced at a lower [14C]DCVC dose (5 mg/kg body wt). Localization of [14C]DCVC was also observed in the liver, exocrine pancreas, and stomach (fundal part), although at a lower level than in the kidney. While the low dose (5 mg/kg body wt) produced a moderate lesion in the straight proximal tubules 24 hr after DCVC, the high dose (25 mg/kg body wt) not only induced a more pronounced lesion in this tubular segment but also extended the lesion to other tubular segments, including the subcapsular region. The results indicate binding of (a) vinyl-containing metabolite(s) to the straight portion of the proximal tubules, where a primary lesion is subsequently developed. Depending on dose, a "secondary" lesion appears in the subcapsular region, topographically different from the DCVC-binding region.
D000818:Animals; D001345:Autoradiography; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013438:Sulfhydryl Compounds / Q000032:analysis; D014018:Tissue Distribution; D005723:gamma-Glutamyltransferase / Q000032:analysis
D013438:Sulfhydryl Compounds; C039961:S-(1,2-dichlorovinyl)cysteine; D005723:gamma-Glutamyltransferase; D003545:Cysteine