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Seven in vitro enzymatic systems were investigated for the detection of potential cancer chemotherapeutic compounds. The rationale for choosing each enzyme system was that inhibition of the system would have a more adverse effect on the metabolism of the malignant than the normal cell. For each system the validity of the rationale is supported by in vitro evidence, but as yet in vivo evidence is lacking. The following systems were evaluated with a standard series of cancer chemotherapeutic compounds from the CCNSC: lactate,
-glycerophosphate, and malate dehydrogenases, deoxyribose phosphate aldolase, thymidine phosphorylase, glycolysis, and amino acid incorporation into proteins. These in-vitro screens, as set up, distinguished between specific inhibitors for each system involved and compounds that are either specific inhibitors of other systems or are nonspecific in action. The simple and relatively inexpensive in vitro assays permitted their use as primary screens. The concomitant recording of the data on IBM cards facilitated comparisons of in vitro enzyme systems with each other as well as with data from in vivo animal tests.
1 Supported by contract SA-43-ph-1886 from the Cancer Chemotherapy National Service Center (CCNSC), National Cancer Institute, USPHS.
2 Merck Sharp & Dohme Research Laboratories, Division of Merck & Co., Inc., Rahway, New Jersey, and West Point, Pennsylvania.
3 Present address: Department of Pharmacology, Hahnemann Medical College, Philadelphia, Pennsylvania.
4 Present address: Department of Biological Chemistry, Hahnemann Medical College, Philadelphia, Pennsylvania.
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