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Effect of Bleomycin on the Synthesis and Function of RNA¹

Departments of Developmental Therapeutics [M. T. K., L. T. A., G. F. S.] and Biology [C. W. H.], The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

Bleomycin inhibits cellular RNA synthesis and the inhibition is nonspecific. The ratio of polyadenylate- [poly(A)] containing RNA to non-poly(A)-containing RNA in the drugtreated human lymphocytic cells, line Wil₂, was the same as that in untreated cells. Poly(A) RNA isolated from untreated cells was used as a template for reverse transcriptase to synthesize complementary DNA, which was then used as a probe to assay the sequence diversity of poly(A) RNA's from treated and untreated cells. It was found that essentially all of the poly(A) RNA's in the untreated cells were also present in the treated cells.

The effect of bleomycin on the biological activity of messenger RNA (mRNA) was tested with globin mRNA in a wheat germ embryo translation system. Although bleomycin inhibited protein synthesis at high concentrations, the inhibition was not due to a modification of mRNA. This was evidenced by the fact that no decrease in the ability of mRNA to function in the test system was found when globin mRNA was pretreated with high concentrations of bleomycin followed by removal of the drug.

¹ This investigation was supported in part by Grants CA 11520 and CA 13246 awarded by the National Cancer Institute, Departments of Health, Education and Welfare, and Grant G-441 from the Robert A. Welch Foundation.

² Supported by a Rosalie B. Hite Fellowship.

³ To whom requests for reprints should be addressed.

Received 10/ 8/76. Accepted 2/ 1/77.