For comparison of tumor cells with corresponding normal cells it seems particularly pertinent to have information concerning content and metabolic activities of various protein fractions of the nuclei of these cells. Notable progress in fractionation of proteins of the nuclei of normal cells has been summarized by Allfrey et aZ.( 1). Daly et a L ( 2 ) and Smellie et a L ( 3 ) have determined the relative incorporation of labelled glycine into several protein fractions of the nuclei of liver cells, and Allfrey et a L ( 4 ) have made a similar study of protein fractions of the nuclei of calf thymus cells. In the present study the proteins of the Auclei of normal liver cells of the adult rat are compared from a quantitative standpoint with corresponding fractions of the nuclei of a transplanted liver tumor. These fractions were analyzed for glycine, and the incorporation of g1y~ine-l-C~~ was determined.Methods. The tumor used in these experiments originated in the liver of a rat which had been fed p-dimethylaminoazobenzene. In the fourth-transplant generation it was implanted by trocar into the axillary region on both sides of male albino rats (Carworth Farms) maintained on Purina dog chow ad libitum. When the tumors had attained a size of approximately 10 g , the rats, which at this time were of about adult size, were given an intraperitoneal injection of g1y~ine-l-C~~ (14 pc/lOO g body weight) in 0.9% saline. Twenty hours thereafter the rats were sacrificed, and the livers and tumors were removed quickly for the isolation of nuclei by the method of Hogeboom et aZ.(5). The total cytoplasmic fractions of the homogenates of
A study was made of the possible mechanisms of inhibition of the growth of Ehrlich asciies carcinoma by the following pyrimidine analogs: ó-flnorooroiic aldehyde (III), 2-thio-5-fluoroorotic aldehyde (IV), 2-meihvlmercapto-ó-fluoroorotic aldehyde (Y), 2-ethylmercapto-ó-fluoroorotic aldehyde (VI), and 0-(2-thio-4-o.xy-ti-pyrimidylmethylidene)-5'-oxo-2'-phenyloxazoline (MI). Among the pyrimidine analogs tested only VI and YII inhibited incorporation of orotic acid-6-1JC into RNA and DNA in vitro. The inhibition of the conversion of orotic acid to orotidylic acid was the main cause of the inhibition of RNA synthesis. The incorporation of formate-HC into purines of RNA was inhibited by the compounds III, IV, Y, and M in contrast to the lack of effect of 5-fluorouraeil (FU). These analogs, III-YI, also inhibited incorporation of formate-HC and thymidine-3II into DNA-thymine, but FU inhibited formate incorporation only. The incorporation of formate-14!', glycine-l-14C, and phenyIalamne-l-14C into proteins was inhibited markedly by the analogs III-YI and 2-thioorotic aldehyde (I).We have previously reported on the synthesis of antitumor derivatives of (S-pyrimidinecarbo.xaldehydes: Kchiff bases, hydrazones,3 methvlidenerhodanines, aketo acids, -thioketo acids, and -oximino acids.4
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.