The interaction of chromium with nucleic acids

Area of Science:

• Biochemistry
• Toxicology
• Molecular Biology

Background:

• Chromium(VI) is a known carcinogen.
• The interaction mechanisms between chromium and nucleic acids are not fully understood.

Purpose of the Study:

• To investigate the binding of chromium to DNA and RNA.
• To elucidate the role of metabolic activation in chromium-nucleic acid interactions.
• To explore the implications for chromium(VI) carcinogenicity.

Main Methods:

• In vitro incubation of calf thymus DNA and homopolyribonucleotides with rat liver microsomes, NADPH, and chromium(VI) or chromium(III).
• Quantification of chromium and protein binding to nucleic acids.
• Comparison of binding affinities under different conditions (e.g., presence/absence of microsomes and NADPH, native vs. denatured DNA).

Main Results:

• Chromium(VI) significantly binds to both native and denatured DNA in the presence of microsomes and NADPH, with denatured DNA showing higher binding.
• Chromium binding to DNA correlates with increased protein binding.
• Chromium(III) shows minimal binding to DNA, unaffected by the microsomal system.
• For ribopolymers, chromium and protein binding follows the order: poly(G) > poly(A) ≈ poly(C) ≈ poly(U).
• Metabolic activation of chromium(VI) is crucial for significant nucleic acid interaction.

Conclusions:

• Metabolic reduction of chromium(VI) is necessary for its interaction with nucleic acids.
• Metabolically derived chromium preferentially binds to guanine.
• Chromium-induced DNA-protein cross-links are formed, contributing to the proposed mechanism of chromium(VI) carcinogenicity.