Characterization of nonmutagenic Cr(III)-DNA interactions

Area of Science:

• Environmental toxicology
• Molecular toxicology
• Genetics

Background:

• Carcinogenic chromium(VI) exposure leads to chromium(III)-DNA adducts, but their role in tumor formation is unknown.
• Chromium(III) complexes are used to model chromium(VI) metabolism products for mechanistic studies.

Purpose of the Study:

• To characterize chromium(III) complex interactions with DNA.
• To evaluate chromium(III) complexes as models for chromium(VI)-induced DNA damage.

Main Methods:

• Compared DNA reactivity of chromic chloride hexahydrate (CrCl(3)) and sodium bis(l-cysteinato)chromium(III) dihydrate (Cr(cys)(2)(-)) with cis-platin.
• Assessed DNA unwinding via gel electrophoresis mobility shifts.
• Measured Cr-DNA adducts in CHO AA8 cells and mutagenicity using the hypoxanthine-Guanine phosphoribosyltransferase assay.

Main Results:

• CrCl(3) caused minimal DNA unwinding (1-2 degrees) compared to cis-platin; Cr(cys)(2)(-) showed weak DNA interaction.
• CrCl(3) produced Cr-DNA adducts in cells at levels similar to Cr(VI), while Cr(cys)(2)(-) did not.
• CrCl(3)-induced lesions were not mutagenic in the tested assay.

Conclusions:

• CrCl(3) may form non-distorting Cr(III)-DNA adducts, possibly via backbone association.
• The models CrCl(3) and Cr(cys)(2)(-) may not accurately represent Cr(III) products from Cr(VI) metabolism.
• Further molecular understanding of Cr(III)-DNA interactions is needed to determine their role in Cr(VI)-induced carcinogenesis.