ROLE OF SOLUBILIZED CHROMIUM IN THE INDUCTION OF MORPHOLOGICAL TRANSFORMATION OF SYRIAN-HAMSTER EMBRYO (SHE) CELLS BY PARTICULATE CHROMIUM(VI) COMPOUNDS

Chromium(VI) compounds-Ca, Sr, Zn and Pb chromates-were studied for cytotoxicity and morphological transformation in Syrian hamster embryo (SHE) cells in relation to their solubilization in cell culture conditions and intracellular Cr concentration. Ca, Sr and Zn chromates were completely solubilized after 1 day of incubation in cell cultures; for Pb chromate, 20-36% Cr was solubilized only after 7 days. In two parallel transformation assays, the SHE cells were treated with suspensions or with corresponding supernatants (containing only solubilized Cr) of these compounds. A statistically significant relationship was observed between the Cr treatment concentration and the amount of Cr per cell, irrespective of the compound (except suspensions of Pb chromate). The cytotoxicity was due to extracellular solubilized chromium because treatments with either supernatants or suspensions of Ca, Sr and Zn chromates gave the same LC50 of 0.31 +/-0.01-mu-g Cr/ml. A clear dose-response relationship was observed for the induction of morphological transformation for each compound, either previously solubilized or in suspension. The expression of the transformation frequencies as a function of the Cr concentration/cell revealed that (i) the transformation frequency is dependent on the Cr concentration/cell irrespective of the Cr compound Ca, Sr or Zn chromate, (ii) the transformation frequency induced by solubilized Pb chromate is higher than that induced by the other compounds at the same concentration of Cr/cell. A double treatment with solutions of Cr and Pb at corresponding concentrations induced the same transformation frequency as the solubilized Pb chromate. The results show that the solubilization of particulate Cr(VI) compounds is a critical step for their cytotoxic and transforming activities; the intracellular soluble Cr is the sole causative agent of the transforming activity of Ca, Sr and Zn chromates, while Pb appears to act synergistically with Cr in inducing the transformation by Pb chromate.