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Activities of DNA Nucleotidyltransferases and Other Enzymes in Cell-free Preparations from Hepatomas of Different Growth Rates¹

Kettering-Meyer Laboratory, Southern Research Institute,² Birmingham, Alabama, and Laboratory of Biochemistry, National Cancer Institute, NIH, Bethesda, Maryland

Cell-free preparations were made from host livers and the following rat hepatomas, which are listed in the order of increasing rates of growth: Morris Hepatoma 5123-C, Reuber Hepatoma H-35, Morris Hepatoma 7288-C, Morris Hepatoma 3683, and Novikoff hepatoma. These preparations were assayed for replicative DNA nucleotidyltransferase and terminal DNA nucleotidyltransferase by using them in incubation mixtures containing ¹⁴C-labeled deoxyribonucleoside phosphates in the presence and absence of the other 3 nonradioactive deoxyribonucleoside phosphates. Both the monophosphates and the triphosphates were used as substrates. Quantitative data for the simultaneous degradation of the substrates, phosphorylation of the monophosphates, and incorporation of ¹⁴C into the acid-insoluble material were obtained. It was concluded that degradative enzymes did not lower the concentrations of the substrates to levels that were rate limiting for the synthesis of DNA and that deoxyribonucleotide kinases were also probably not limiting enzymes. There was a good correlation between the rates of growth of the tumors and the activities of replicative and terminal DNA nucleotidyltransferases in the cell-free preparations—the preparations obtained from the more rapidly growing tumors had the higher activities of each of these enzymes. Therefore, even though various controls might function along the metabolic pathways leading to deoxyribonucleoside triphosphates and thus limit the quantities of substrates for the synthesis of DNA in the slowly growing tumors and host liver, there is also a limitation that is effective at the level of the formation of polydeoxyribonucleotides.

¹ This work was supported by the Cancer Chemotherapy National Service Center, National Cancer Institute, under NIH Contract No. PH43-66-29 and by grants from the Charles F. Kettering Foundation and the Alfred P. Sloan Foundation.

² Affiliated with Sloan-Kettering Institute for Cancer Research, New York, N. Y.

Received 4/13/66. Accepted 6/27/66.