Urinary metallothionein and tissue metal levels of rats injected with cadmium, mercury, lead, copper or zinc.

Since Cd exposure results in a dose dependent increase in metallothionein level in urine, the present investigation was conducted to examine whether exposure to other divalent cations would also cause an elevation in urinary metallothionein. Female Sprague-Dawley rats were injected subcutaneously with either saline, 5 mumol/kg/day of CdCl2, HgCl2, Pb(C2H3O2)2, CuSO4 or ZnCl2 for 5 days. Significant increases in hepatic Cu levels in rats treated with not only Cu, but also Zn, Cd, or Hg, and in hepatic Zn levels in rats treated with Zn or Cd were noted. Similarly, renal Cu and Zn levels were elevated significantly in all groups except the Pb-injected group. These increases in tissue metal levels were presumably due to induction of metallothionein. The urinary metallothionein level in control rats on day 0, determined by radioimmunoassay, was 0.85 +/- 0.17 mg/g creatinine. There was no significant change in urinary metallothionein level in rats given up to 5 injections of saline or Pb. Hg-injected rats showed 25-fold increase in urinary metallothionein after 5 injections, whereas Cd-injected rats had 9-fold increase. There were also 2- and 3-fold increases of urinary metallothionein by Cu and Zn treatments for 5 days, respectively. Thus, urinary metallothionein levels were elevated in response to Cd, Hg, Cu and Zn, but not Pb; Hg had the most profound effect at equimolar doses.