Polyinosinic-polycytidylic acid: inhibition of cell proliferation in carcinogen-treated epidermis and in carcinogen-induced skin tumors in mice.

After administration of the synthetic double-stranded RNA polyinosinic with polycytidylic acid (poly l with poly C) to hairless mice, cell proliferation kinetics were studied in normal epidermis, in epidermis initiated with 3-methylcholanthrene (MCA), in hyperplastic epidermis treated topically with MCA for 15 weeks, and in MCA-induced skin tumors. Poly l with poly C did not influence the mitotic rate or the transit of cells from the G1 phase to the S phase in normal mouse epidermis. Pretreatment of poly l with poly C inhibited cell proliferation in mouse epidermis initiated with MCA for at least 24 hours. In mouse epidermis made hyperplastic by repeated applications of MCA. Poly L with poly C inhibited G1 cells from starting DNA synthesis. Skin tumor DNA synthesis was also altered after poly l with poly C administration. After a short period of enhanced 3-methylthymidine incorporation, tumor DNA synthesis decreased to less than half the control value. The results indicated thatthe antitumorigenic effect of poly l with poly C could be related to its influence on cell proliferation.