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Nogalamycin Effects in Rat Liver: Inhibition of Tryptophan Pyrrolase Induction and Nucleic Acid Biosynthesis¹

Research Laboratories, The Upjohn Company, Kalamazoo, Michigan

In partially-hepatectomized and sham-operated rats, nogalamycin exhibits the same general patterns of inhibitory activity which are seen with actinomycin D: (a) Marked inhibition of orotate incorporation into RNA; (b) marked inhibition of thymidine incorporation into DNA at high drug levels only; and (c) little or no inhibition of valine incorporation into protein. Nogalamycin inhibited completely the hydrocortisone-induced increase in tryptophan pyrrolase activity but did not affect the substrate-induced increase. The inhibitory effects of nogalamycin administration were not detected after a 24-hr period. These results are compatible with the suggestion that nogalamycin interferes primarily with RNA, including messenger RNA, synthesis.

¹ This work was supported in part by Contract No. SA-43-pH-1933, Cancer Chemotheraphy National Service Center.

Received 3/31/66. Accepted 6/17/66.