The interaction of chromium with nucleic acids.
Native and denatured calf thymus DNA, and homopolyribonucleotides were compared with respect to chromium and protein binding after an in vitro incubation with rat liver microsomes, NADPH, and chromium (VI) or chromium (III). A significant amount of chromium bound to DNA when chromium (VI) was incubated with the native or the denatured form of DNA in the presence of microsomes and NADPH. For both native and denatured DNA the amount of protein bound to DNA increased with the amount of chromium bound to DNA. Denatured DNA had much higher amounts of chromium and protein bound than native DNA. There was no interaction between chromium(VI) and either form of DNA in the absence of the complete microsomal reducing system. The binding of chromium(III) to native or denatured DNA was small and relatively unaffected by the presence of microsomes and NADPH. The binding of chromium and protein to polyriboadenylic acid (poly(A], polyribocytidylic acid (poly(C], polyriboguanylic acid (poly(G] and polyribouridylic acid (poly(U] was determined after incubation with chromium(VI) in the presence of microsomes and NADPH. The magnitude of chromium and protein binding to the ribopolymers was found to be poly(G) much greater than poly(A) approximately equal to poly(C) approximately equal to poly(U). These results suggest that the metabolism of chromium(VI) is necessary in order for chromium to interact significantly with nucleic acids. The metabolically-produced chromium preferentially binds to the base guanine and results in DNA-protein cross-links. These findings are discussed with respect to the proposed scheme for the carcinogenicity of chromium(VI).
D000818:Animals; D001711:Biotransformation; D002857:Chromium / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009691:Nucleic Acid Denaturation; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland
D002857:Chromium; D009249:NADP; D004247:DNA