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Title	Interaction of the antitumor platinum compound, cis-dichloro (dipyridine) platinum (II) (cis-PPC) with precursors of cellular biopolymers and other small molecules
Author	Morris, C. (Carl)
Date	1974
Affiliation/College	College of Graduate Studies
Department	Pharmacology
Extent	106 leaves; 29 cm
Subject.MeSH	Organoplatinum Compounds--pharmacology Academic Dissertations
Collection	MUSC Theses and Dissertations
Contributing Institution	Waring Historical Library (MUSC)
Rights	Copyright is held by the author.
Language	English
Type	Text
Format	application/pdf
Media Type	Manuscripts
Resource Identifier	mtd1974_morris_cr
Abstract	Cis-dichloro([G-3H]dipyridine)platinum(II) (cis-PPC-3H) was observed to interact with several amino acids and nucleotides under conditions of equilibrium dialysis. Considerable interaction between the negatively charged polymers--poly-L-g1utamate (poly-L-Glut), poly-L-aspartate (poly-L-Asp), and calf thymus DNA--was observed. The positively-charged polymers--poly-L-lysine (poly-L-Lys), po1y-Larginine (poly-L-Arg), and calf thymus histones--repelled cis-PPC-3H. The association of calf thymus histones with DNA reduced by over 50% the extent of subsequent cis-PPC-3H association to DNA. Cis-PPC binding to Ehrlich ascites tumor cells (EATC) and human or bovine lymphocytes was not affected by low temperature; however, cis-PPC-3H binding to EATC was affected by the incubation media and the pH. The extent of cis-PPC_3H binding to EATC was reduced by preexposure of the cis-platinum congener and several L-amino acids; however, the apparent amino acid-cis-PPC interaction did not affect the amino acid uptake into EATC to any appreciable extent. Interaction of ornithine (Orn) with cis-PPC did not affect the functional capacity of Orn to serve as a substrate for putrescine synthesis. Administration of cis-PPC to mice bearing l-day-old L1210 leukemia prevented the subsequent rise in spleen or liver ornithine decarboxylase activity which occurs predictably in untreated L1210- bearing mice. Of the tissues evaluated, urinary bladder had the highest ODC activity per gm (wet wt). Therapeutic implications as well as additional studies indicated on the basis of data reported here are discussed.

Interaction of the antitumor platinum compound, cis-dichloro (dipyridine) platinum (II) (cis-PPC) with precursors of cellular biopolymers and other small molecules

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