Detection of cadmium exposure in rats by induction of lymphocyte metallothionein gene expression.
The induction of metallothionein (MT) gene expression in lymphocytes of rats was determined in order to detect exposure in vivo to cadmium. Both acute and chronic CdCl2 exposures resulted in the induction of the MT-1 gene in lymphocytes as measured by standard RNA Northern blot analysis. Twenty-four hours following an ip injection of 3.4 mg/kg CdCl2, a ninefold increase in MT gene expression was observed in lymphocytes, as well as five- and sevenfold increases in liver and kidney, respectively. Oral exposure of rats to 1-100 ppm CdCl2 via drinking water resulted in an approximate twofold enhanced MT signal in lymphocytes after 6 wk, and a threefold increase after 13 wk of exposure to 100 ppm Cd. No increases in lymphocyte MT gene expression were observed after 3 wk of Cd exposure. Liver MT gene expression was substantially induced following chronic Cd exposure, while kidney was not, although this organ had a higher basal expression of the MT-1 gene. Analysis of tissue Cd burdens demonstrated a dose-response Cd accumulation in liver and kidney, but only kidney burdens increased substantially with prolonged Cd exposure. These results demonstrate the utility of lymphocyte gene expression assays to detect in vivo toxicant exposure, and thus their applicability as molecular biomarker assays for human exposure assessment.
Cosma
G N
GN
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Currie
D
D
Squibb
K S
KS
Snyder
C A
CA
Garte
S J
SJ
D000818:Animals; D015152:Blotting, Northern; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D019256:Cadmium Chloride; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D012313:RNA / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013054:Spectrophotometry, Atomic
D002104:Cadmium; D012313:RNA; D008668:Metallothionein; D019256:Cadmium Chloride