Hneihen A S, Standeven A M, Wetterhahn K E
Department of Chemistry, Dartmouth College, Hanover, NH 03755.
Carcinogenesis. 1993 Sep;14(9):1795-803. doi: 10.1093/carcin/14.9.1795.
The binding of CrCl3.6H2O, Cr(NO3)3.9H2O, [Cr(L-His)2] (NO3)3.H2O, [Cr(L-Cys)(L-His)].3.5H2O, [Cr(L-His)(D-Pen)].H2O, Na[Cr(L-Cys)2].2H2O, K2[Cr(GS)2].3H2O, Na2-CrO4.4H2O, and Na2Cr2O7.2H2O to salmon sperm nuclei and nuclear DNA was determined. The Cr(III)-amino acid complexes and Cr(VI) exhibited significantly lower Cr-nuclei and Cr-DNA binding levels relative to the inorganic complexes CrCl3.6H2O and Cr(NO3)3.9H2O. The binding of CrCl3.6H2O, Cr(NO3)3.9H2O and Na2Cr2O7.2H2O to salmon sperm nuclei and nuclear DNA in the presence of rat lung cytosol was determined under the same conditions. For those complexes studied in both buffer and cytosol, the Cr-DNA binding levels for Cr(III) complexes were higher in buffer than in cytosol, while a relatively higher binding level was observed for Cr(VI) in cytosol than in buffer. Slightly lower nuclear protein levels were present in Cr(VI) incubations than in Cr(III) incubations with nuclei both in the presence and the absence of cytosol. The relative binding of CrCl3.6H2O, Cr(NO3)3.9H2O, Cr(L-His)23.H2O, [Cr(L-Cys) (L-His)].3.5H2O, [Cr(L-His)(D-Pen)].H2O, Na[Cr(L-Cys)2].2H2O and Na2CrO4.4H2O to isolated calf thymus DNA in buffer was also determined. Positively charged, labile inorganic Cr(III) complexes, CrCl3.6H2O and Cr(NO3)3.9H2O, exhibited higher binding to DNA than [Cr(L-His) (D-Pen)].H2O, and no binding to DNA was observed with Cr(VI) and the other neutral, positively and negatively charged, inert Cr(III)-amino acid complexes. Although labile aquo chromium(III) complexes are quite reactive with DNA, the reactivity of chromium(III), formed upon intracellular reduction of carcinogenic chromium(VI), toward DNA will be diminished by complexation with cellular proteins, peptides and amino acids.
测定了三氯化铬六水合物（CrCl₃·6H₂O）、硝酸铬九水合物（Cr(NO₃)₃·9H₂O）、Cr(L-组氨酸)₂₃·H₂O、[Cr(L-半胱氨酸)(L-组氨酸)]·3.5H₂O、[Cr(L-组氨酸)(D-青霉胺)]·H₂O、Na[Cr(L-半胱氨酸)₂]·2H₂O、K₂[Cr(谷胱甘肽)₂]·3H₂O、重铬酸钠四水合物（Na₂CrO₄·4H₂O）和重铬酸钠二水合物（Na₂Cr₂O₇·2H₂O）与鲑鱼精细胞核及核DNA的结合情况。相对于无机配合物CrCl₃·6H₂O和Cr(NO₃)₃·9H₂O，Cr(III)-氨基酸配合物和Cr(VI)表现出显著更低的Cr-核及Cr-DNA结合水平。在相同条件下，测定了CrCl₃·6H₂O、Cr(NO₃)₃·9H₂O和Na₂Cr₂O₇·2H₂O在大鼠肺细胞溶质存在下与鲑鱼精细胞核及核DNA的结合情况。对于在缓冲液和细胞溶质中都进行研究的那些配合物，Cr(III)配合物的Cr-DNA结合水平在缓冲液中高于在细胞溶质中，而Cr(VI)在细胞溶质中的结合水平相对于缓冲液中则较高。在有和没有细胞溶质存在的情况下，Cr(VI)孵育时的核蛋白水平略低于Cr(III)与核孵育时的水平。还测定了CrCl₃·6H₂O、Cr(NO₃)₃·9H₂O、Cr(L-组氨酸)₂₃·H₂O、[Cr(L-半胱氨酸)(L-组氨酸)]·3.5H₂O、[Cr(L-组氨酸)(D-青霉胺)]·H₂O、Na[Cr(L-半胱氨酸)₂]·2H₂O和Na₂CrO₄·4H₂O与缓冲液中分离的小牛胸腺DNA的相对结合情况。带正电荷、不稳定的无机Cr(III)配合物CrCl₃·6H₂O和Cr(NO₃)₃·9H₂O与DNA的结合高于[Cr(L-组氨酸)(D-青霉胺)]·H₂O，且未观察到Cr(VI)及其他中性、带正电荷和带负电荷的惰性Cr(III)-氨基酸配合物与DNA的结合。尽管不稳定的水合铬(III)配合物与DNA反应性很强，但致癌性铬(VI)在细胞内还原形成的铬(III)与DNA的反应性会因与细胞蛋白质、肽和氨基酸的络合而降低。
