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supernatants by a modified cadmium saturation method as described previously. Zn, Cu and
Cd were detected in tissue homogenates by atomic emission spectroscopy with inductively
coupled plasma excitation or atomic absorption spectroscopy after wet ashing of the
samples at 140°C with nitric acid.
RESULTS
MT was detected in all human tissues investigated. The highest MT tissue levels were found
in kidney cortex. In all tissues except brain and small intestine, human samples showed
higher MT levels than those of rats. Particularly in liver and kidney, human MT levels
exceeded those of rats about 25- and 10-fold, respectively.
Human tissues showed moderate differences in their Zn or Cu levels whereas regarding Cd
levels pronounced variations were observed. The highest Cd concentrations (29.7 ±13.6
µg/gwet weight) were observed in the kidney cortex.
In most human and rat tissues the levels of Zn and Cu were approximately similar
within a factor of 2. In comparison with the very low levels of Cd in rat tissues, the Cd
levels of all human tissues were remarkably higher. The Cd levels of all rat tissues were
lower than the detection limit of 20 ng Cd/g tissue wet weight. In human liver, positive
relationships between the concentrations of both Zn and Cu and the amount of MT were
observed. The regression coefficients were r = 0.871 (MT (µg) = 9.8 Zn (µg) - 257) and r =
0.955 (MT (µg) = 100 Cu (µg) — 359), respectively.
In human kidney cortex, a positive relationship was observed between Cd and MT with
a regression coefficient of r = 0.779 (MT (µg) = 13.4 Cd (µg) + 98.5). Metallothionein
levels in human kidney and liver were not significantly correlated.
DISCUSSION
MT was detected in all rat and human tissues investigated. The rat data confirm earlier
findings of others, and us although lower levels of brain MT were obtained with a
radioimmunoassay. In most human tissues higher levels of MT were observed than in rats.
Moreover, human MT levels, particularly in liver and kidney showed greater interindividual
variations, e.g., the concentrations of human hepatic MT varied between 11 and 1000 µg/g.
The extraordinarily high levels of MT in human kidney and liver may reflect a different
transcriptional control of the protein, the occurrence of multiple subtypes of human MT
isoforms, or the high exposure of man to environmental metals. In accordance with the
latter, levels of zinc, copper and particularly cadmium in human liver and levels of zinc and
cadmium in human kidney clearly exceeded those of the rat. With a ratio of 7 mol Cd per
mol of MT, MT of human liver and kidney cortex has the capacity to bind total tissue
cadmium. This supports the assumed protective role of MT in the detoxification of Gd.
However, in the renal cortex of both smokers and non-smokers, MT was shown to bind
about 50% of tissue Cd only. The remaining non-MT Cd may represent a significant toxic
potential. Zinc, copper and cadmium are potent inducers of MT in animal tissues. Although
there is no clear evidence for the induction of MT by these metals in human tissues, the
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