Add time:09/05/2019         Source:sciencedirect.com

The molecular effects of the pyrrolopyrimidine analogs, SANGIVAMYCIN (cas 18417-89-5) and thiosangivamycin, on RNA and DNA synthesis were examined in L1210 cells in vitro. Pretreatment of cells for 30 min with either sangivamycin or thiosangivamycin resulted in a median inhibitory dose of 1 × 10−5 M and 2 × 10−5 M, respectively, for RNA synthesis. Sangivamycin did not inhibit DNA synthesis at comparable concentrations, while thiosangivamycin inhibited DNA synthesis by 20–35 per cent. Extending preincubation times with either drug to 1 hr resulted in decreased inhibition of RNA synthesis. Sangivamycin and thiosangivamycin also inhibited the transcription of nuclear RNA with 32P as precursor. Incorporation of 32P into AMP was reduced by both drugs to a much greater extent that the labeling of GMP, CMP, or UMP of alkaline hydrolysates of total nuclear RNA. Thiosangivamycin also significantly reduced methylation in nuclear rRNA. Neither drug affected the concentration or specific radioactivity of S-adenosyl-l-methionine or UTP. Sangivamycin and thiosangivamycin inhibited the syntheses of nuclear rRNA, non-poly(A) heterogeneous RNA and poly(A) heterogeneous RNA to equal extents, but the potency of sangivamycin was approximately 10-fold less than that of thiosangivamycin. These results suggest that sangivamycin and thiosangivamycin act as adenosine analogs to inhibit the transcription of all forms of nuclear RNA in L1210 cells.

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