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Molecular Pharmacology, Vol 15, 165-173, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Polyinosinic Acid-Polycytidylic Acid and Its Mismatched Analogues: Differential Effects on Human Cell Function

JUDITH A. O’MALLEY 1, SUSAN S. LEONG 1, JULIUS S. HOROSZEWICZ 1, WILLIAM A. CARTER 1, JAMES L. ALDERFER 2, and PAUL O. P. TS’O 2

1 Department of Medical Viral Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263
2 Division of Biophysics, Department of Biochemical and Biophysical Studies, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205

This study extends, into human systems, earlier work with mismatched analogues of polyinosinic acid-polycytidylic acid, rIn·rCn, which were consistently shown to be less toxic than rIn·rCn in various lower animal systems. We studied the mismatched analogues in a variety of human cells, hoping thereby to obtain an index of possible therapeutic efficacy and toxicity which might be observed in intact man. At doses which induce antiviral activity, the mismatched analogues of rIn·rCn, do not detrimentally affect various cell systems such as the cloning of human myeloid colony forming cells. With suspensions of human splenocytes, mismatched inducers are much less mitogenic than rIn·rCn, and the mismatched inducers show less effect on retarding the growth of human fibroblastic cells.

Note:
ACKNOWLEDGMENTS Dr. Leonard Schechtman carried out the experiments concerned with cell growth of the fibroblast cultures.

Submitted on March 31, 1978
Accepted on September 8, 1978






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