The aim of this work is to study the accumulation in HepG2 cells of two ess
ential metals with toxic potency and to analyse the induction of the heat s
hock protein 70 kDa (hsp70) consequent to metal exposure. Cu and Zn were th
e metals considered and were analysed both as single compounds and in combi
nation in order to evidence synergic effects of the mixture. The use of Hep
G2 cells provided an in vitro system that retains morphological and metabol
ic properties and the expression of specific genes typical of liver parench
ymal cells. Moreover, the hepatic cells represent a suitable model for thei
r susceptibility to metal toxicity since liver, gastrointestinal tract and
renal tubular cells are involved in the uptake, transport, detoxification a
nd secretion of these compounds. The uptake of Cu and Zn followed a time-de
pendent accumulation when they were used separate. The combination of the t
wo metals produced a higher accumulation of Zn. The stress protein hsp70 wa
s expressed before the metals accumulated within the cells, as shown by the
measures obtained with the ICP-AES technique. Moreover, the accumulation o
f hsp70 by a sublethal shock provided a protective mechanism against metal
cytotoxicity. (C) 2001 Elsevier Science Ltd. All rights reserved.