Poly I-Mercapto Poly C: antiviral, anticellular, and pharmacologic effects.
Thiolation of position 5 of some of the cytosine bases in polycytidylic acid results in the formation of mercaptopolycytidylic acid (MPC). Annealing of MPC to polyinosinic acid (Poly I) results in the formation of double-stranded Poly I-MPC. In this study we investigated the interferon inducing ability, in vivo toxic effects, effect on DNA synthesis, and the effects in human tumor cell lines of Poly I-MPC. Poly I-MPC was capable of inducing human alpha, beta and gamma interferons in the appropriate cell systems. In vivo toxicity was measured in mice, guinea pigs, and rabbits according to FDA guidelines. Weight loss and lethal and pyrogenic effects were markedly lower in Poly I-MPC treated animals than in those that received unmodified Poly I-Poly C. In contrast to the lack of an effect of Poly I-Poly C in human lymphocytes, Poly I-MPC inhibited DNA synthesis. It also inhibited colony formation and was cytotoxic in several human tumor cell lines. Poly I-MPC's ability to induce human alpha, beta and gamma interferons, to inhibit DNA synthesis and its effects in human tumor cell lines demonstrate the potential of this drug for future clinical studies, both as an antiviral and antitumor agent.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000473:pathology; D006168:Guinea Pigs; D006801:Humans; D007369:Interferon Inducers; D007370:Interferon Type I / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D011070:Poly I-C / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007369:Interferon Inducers; D007370:Interferon Type I; C043612:poly I-5-mercapto-poly C; D007371:Interferon-gamma; D004247:DNA; D011070:Poly I-C