Kinetics of the early subcellular distribution of cadmium in rat hepatocytes.
The kinetics of the early subcellular distribution of cadmium (Cd) was characterized in primary cultures of rat hepatocytes exposed to 10, 50 and 100 microM Cd in a serum-free WME medium for 10, 30 or 60 min. Our results demonstrate a time- and concentration-dependent increase in Cd content with the highest metal concentration measured in the cytosol, whereas the lowest was observed in the mitochondria. With the exception of early localization in the plasma membrane, Cd concentrations in fractions were characterized by the following decreasing order of magnitude: cytosol > low density molecules approximately nuclei > lysosomes approximately mitochondria. We also found evidence for: (i) a two-step process for Cd distribution in the nuclei and mitochondria; and (ii) a time-dependent 'slow' process of transfer from the plasma membrane to the cytosol. Saturation in Cd uptake was observed at 50 microM in most cell fractions at 10 and 30 min, except for the plasma membrane. The lack of apparent saturation for Cd accumulation at 60 min was not related to an increase in metallothionein synthesis. Altogether, our data provide insights into the dynamics of transfer between intracellular compartments, and allow a better identification of the organelles that are the most subjected to Cd toxicity for early exposure conditions.
Diep
Pham T N
PT
Department de chimie, Université dal Québec à Montréal, C.P. 8888, Succ. centre-ville, Montréal, Québec, Canada H3C 3P8.
Denizeau
Francine
F
Jumarie
Catherine
C
D000818:Animals; D002104:Cadmium / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008668:Metallothionein / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D013997:Time Factors
D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein