Exposure to different forms of cadmium in mice: differences in metallothionein and alphafetoprotein mRNA induction in liver and kidney.
Cadmium (Cd) exposure in mice induces transcription of metallothionein (MT) mRNA and protein accumulation in both liver and kidney. Resistance to hepatotoxicity through chronic exposure to heavy metals is the result of this induction. However, the same chronic exposure results in damage to kidney. We report here that acute exposure of mice to Cd as cadmium sulfate (CdSO4), which resulted in preferential accumulation of metal in liver, or Cd-metallothionein (CdMT), which resulted in preferential metal accumulation in kidney, induced MT mRNA accumulation in both liver and kidney. However, MT mRNA accumulated to a level twofold higher in liver than in kidney in response to CdSO4. Equivalent doses of CdMT induced MT mRNA accumulation to an equal degree in kidney and liver. While MT mRNA accumulation in kidney was directly proportional to the amount of cadmium in the organ, this was not the case in liver. There, liver MT mRNA was elevated in the absence of elevated tissue cadmium levels. Interestingly, CdMT induced alphafetal protein (AFP) mRNA accumulation in kidney, but not liver. It appears that (a) maximal MT mRNA accumulation in kidney is less than in liver, and (b) liver is capable of accumulating MT mRNA in response to even very low cadmium exposure that may not result in elevated tissue cadmium.
Koropatnick
J
J
Department of Oncology, University of Western Ontario, London, Canada.
Cherian
M G
MG
D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D019187:Cadmium Compounds; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000633:toxicity; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D013431:Sulfates; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
D019187:Cadmium Compounds; D012333:RNA, Messenger; D013431:Sulfates; D000509:alpha-Fetoproteins; C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; C037123:cadmium sulfate