Direct interaction with cellular targets as the mechanism for chromium carcinogenesis.

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 CrC13) 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.