Soluble vs insoluble hexavalent chromate

Soluble CaCrO₄ and insoluble PbCrO₄ were tested for induction of mutation to 6-thioguanine (base-substitution, deletion, addition, and frameshift mutations) or ouabain (base-substitution mutations) resistance in Chinese hamster ovary cells and morphological transformation in C3H/101/2 mouse embryo cells. CaCrO₄ induced dose-dependent cytotoxicity and mutation to 6-thioguanine resistance, but did not induce mutation to ouabain resistance or morphological transformation. Highly cytotoxic amounts of CaCrO₄ induced conversion of 10T1/2 cells to adipocytes, but cell lines derived from such cells were not transformed. PbCrO₄ was not mutagenic in either mutation assay but induced a dose-dependent, low frequency of focus formation. Cell lines established from these foci had a 3–5-fold increased saturation density, grew in soft agarose, and were tumorigenic in nude mice. Chronic exposure to CaCrO₄ or PbCl₂ did not induce transformation, PbCl₂ was inactive even at acutely cytotoxic concentrations, and sequential treatments with CaCrO₄ and PbCl₂ did not induce transformation. Light and scanning electron microscopy showed progressive cytoplasmic engulfment of PbCrO₄ particles and extensive vacuolization of cells in contact with the particles. No particles were observed inside of vacuoles. We suggest that internalization of PbCrO₄ and the associated cellular stress response may be related to PbCrO₄-induced neoplastic transformation of 10T1/2 cells.