Cytotoxicity, apoptosis, and in vitro DNA damage induced by potassium chromate

Cr6+ is a known human cytotoxic and carcinogenic agent that requires intracellular reduction for activation. We have analyzed the cytotoxic and DNA binding properties of K2CrO4 (Cr6+) in comparison with those of Cl3Cr (Cr3+). The results indicate that K2CrO4 exhibits higher cytotoxicity than Cl3Cr in several human and murine cell lines. The cytotoxic activity of K2CrO4 is also indicated by the fact that is able to produce cell killing through apoptosis in cisplatin-resistant cells transformed by H-ras oncogene. Moreover, in vitro DNA binding experiments show that, in the presence of ascorbate (the major intracellular reductant of Cr6+), K2CrO4 induces both interstrand cross-links and strand breaks. Because the chromate anion is by itself unreactive toward DNA, these data suggest that the cytotoxicity of K2CrO4 may be associated with the DNA binding of reactive intermediate chromium species resulting from reduction of Cr6+. (C) 1999 Academic Press.