Direct Interaction with Cellular Targets as the Mechanism for Chromium Carcinogenesis 1

Abstract

The carcinogenic activity of chromium appears to be due to its direct interaction with cellular targets and not to nonspecific solid-state carcinogenesis. Chromium was evaluated at 2 valences, Cr⁺³ (as CrCl₃ and Cr⁺⁶ (as K₂Cr₂O₇), for its toxicity, transforming activity, and ability to induce chromosomal aberrations in tertiary cultures of mouse fetal cells. The ID₅₀ (dose for 50 percent inhibition of cell growth) of Cr⁺³ was approximately 4 times greater than that of Cr⁺⁶ after 96 h of exposure, and about 29 times greater than that of Cr⁺⁶ after 1 h of exposure. At equitoxic concentrations, both chromium valences induced the same degree of morphologic changes and alterations of growth behavior, but Cr⁺⁶ produced more chromosomal aberrations. Using autoradiography in an established cloned line of mouse cells, unscheduled DNA synthesis was observed in cells previously exposed to Cr⁺⁶ but not in cells previously exposed to Cr⁺³.