Search

The effect of Cr(III) on in vitro RNA synthesis directed by DNA and chromatin isolated from mouse liver was investigated in comparison with other inorganic metals. At 1 mM, CrCl3 significantly stimulated RNA synthesis when incubated with DNA or chromatin prior to the addition of Escherichia coli RNA polymerase, while other metals inhibited it. This stimulation by Cr(III) was caused even at 1 muM CrCl3 on either DNA- or chromatin- directed RNA synthesis. The Cr(III)-complexes of DNA and chromatin also showed significantly enhanced template activities. On the other hand, when RNA polymerase was preincubated with Cr(III), a remarkable inhibition was observed in RNA synthesis directed by both DNA and chromatin. In isolated mouse liver nuclei with endogenous RNA polymerases, Cr(III) stimulated Mg2+-activated RNA synthesis but not Mn2r-(NH4)2SO4-activated synthesis. These results suggest that Cr(III) may alter or regulate gene expressions in mammals.

By forming a complex with calf thymus DNA, Cr(III), i.e., CrCl3 and Cr(NO3)3, significantly enhanced its template activity for in vitro RNA synthesis as assayed by 3H incorporation from [5-3H]uridine triphosphate (UTP). The extent of the augmentation in RNA synthesis was proportional to the binding ratio of Cr(III) to the template DNA. K2CrO4, on the other hand, neither bound to DNA nor enhanced its template activity. Experiments using rifampicin and heparin suggested that incorrect and nonviable initiation sites for RNA synthesis became functional in Cr(III)-bound DNA. The incorporation of [γ-32P]adenosine triphosphate (ATP) into RNA synthesized on Cr(III)-bound DNA was 8 to 9 times greater than that on control DNA. This value was much higher than that of the 3H incorporation form [5-3H]UTP, i.e., the incorporation of 32P on Cr(III)-bound DNA was 8 to 9 times greater than of 3H and less than twice that on control DNA. These results suggest that Cr(III) possibly induces the abnormal synthesis of RNA of a very low molecular weight, for most if not all the molecules, by binding to the template DNA.