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DNA Polymerases of Walker 256 Carcinosarcoma

Laboratory of Chemical Pharmacology [T. P. W., K. S., R. H. A.] and Laboratory of Tumor Cell Biology [R. G. S.], National Cancer Institute, NIH, Bethesda, Maryland 20014

Walker 256 carcinosarcoma in rats has been a useful tumor for the evaluation of potential chemotherapeutic agents. Recently, several compounds with proven antiviral activity were also shown to inhibit the growth of Walker 256 carcinosarcoma, suggesting the possibility that an oncogenic virus, through a mechanism such as recruitment, for example, might be an essential factor for the growth of the tumor. In view of the consistent finding of an RNA-directed DNA polymerase associated with RNA tumor viruses, and in an effort to gain a better understanding of the effects of chemotherapeutic agents on this tumor, a study of the DNA polymerases of Walker 256 carcinosarcoma was made. Following extraction, separation, and purification, four distinct DNA polymerase activities were found, including an RNA-directed DNA polymerase as judged by current criteria. The ability of selected antitumor, antiviral, and anti-DNA polymerase compounds to act as inhibitors of these enzymes in vitro was studied. At concentrations equivalent to those producing antitumor effects in vivo, the compounds showed considerable variation in the degree of inhibition of the respective enzymes. None of these compounds caused more than 40% inhibition of the RNA-directed DNA polymerase which suggests that their in vivo antitumor properties were probably mediated through some mechanism of action other than inhibition of this enzyme.

Received 6/29/73. Accepted 11/16/73.