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Transport of Antineoplastic Agents

  • Chapter
Antineoplastic and Immunosuppressive Agents Part I

Abstract

Before an agent can damage a cancer cell, it must be able to pass through the outer cell membrane, also called the plasma membrane. An exception to this rule would be provided by a “membrane-active” compound, which would affect the plasma membrane only and by so doing cause cell death. Antibacterial agents of this type do exist (Hamilton, 1970). One may speculate that highly lipid soluble compounds could be localized in plasma membranes of mammalian cells and thereby seriously alter cellular metabolism. However, most of the antineoplastic agents whose mode of action is understood appear to act somewhere within the cell. A notable exception is provided by asparaginase, which, without entering the cells, causes a critical deficiency of asparagine by cleaving it extracellularly to aspartic acid (Broome, 1968; Suolinna et al., 1971).

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References

  • Askari, A.: Uptake of some quaternary ammonium ions by human erythrocytes. J. gen. Physiol. 49, 1147–1160 (1966).

    PubMed  CAS  Google Scholar 

  • Ballard, P.L., Tomkins, G.M.: Hormone induced modification of the cell surface. Nature (Lond.) 224, 344–345 (1969).

    CAS  Google Scholar 

  • Benedetti, E.L., Emmelot, P.: Structure and function of plasma membranes isolated from liver. In: Dalton, A. J., Haguenau, F. (Eds.): Ultrastructure in biological systems, vol. 4, The Membranes, pp. 33–120. New York: Academic Press (1968).

    Google Scholar 

  • Bennett, L.L., Jr.: Phthalanilides and some related dibasic and polybasic compounds: A review of biological activities and modes of action. Progr. exp. Tumor Res. 7, 259–325 (1965).

    PubMed  CAS  Google Scholar 

  • Bensch, K.G., Simbonis, S., Hill, R.B., King, D.W.: Phagocytosis and cell division. Nature (Lond.) 183, 476–477 (1959).

    CAS  Google Scholar 

  • Ber, R., Griffin, M.J.: Location of hydrocortisone in dividing Hela S3 cells. Fed. Proc. 26, 616 (1967).

    Google Scholar 

  • Bieber, A.L., Sartorelli, A.C.: The metabolism of thioguanine in purine analog resistant cells. Cancer Res. 24, 1210–1215 (1964).

    PubMed  CAS  Google Scholar 

  • Blair, D.G.R., Hebert, G.J.: Uptake of 2, 6-diaminopurine-2-C14 by 2, 6-DAP-sensitive and-resistant L strain mouse cells grown on plastic discs. Canad. J. Physiol. Pharmacol. 48, 791–800 (1970).

    CAS  Google Scholar 

  • Bobinski, H., Stein, W.D.: Isolation of a glucose-binding component from human erythrocyte membranes. Nature (Lond.) 211, 1366–1368 (1966).

    CAS  Google Scholar 

  • Bobzien, W., Goldman, I.D.: The mechanism of methotrexate transport in rabbit reticulocytes. J. clin. Invest. 51, 1688–1696 (1972).

    PubMed  CAS  Google Scholar 

  • Booij, H.L., Bungenberg De Jong, H.G.: Biocolloids and their interactions. Proto-plasmatologia I 2, 142. Springer: Wien 1956.

    Google Scholar 

  • Braganca, B.M., Divekar, A.Y., Vaidya, N.R.: Defective transport of aminopterin in relation to development of resistance in Yoshida sarcoma cells. Biochim. biophys. Acta (Amst.) 135, 937–946 (1967).

    CAS  Google Scholar 

  • Broome, J.D.: Studies on the mechanism of tumor inhibition by L-asparaginase. J. exp. Med. 127, 1055–1072 (1968).

    PubMed  CAS  Google Scholar 

  • Bucknall, R.M., Carter, S.B.: A reversible inhibitor of nucleic acid synthesis. Nature (Lond.) 213, 1099–1101 (1967).

    CAS  Google Scholar 

  • Collins, F.D., Roberts, W.K.: The effect of dimethvl sulfoxide on nucleoside transport in L-cells. Biochim. biophys. Acta (Amst.) 233, 459–464 (1971).

    CAS  Google Scholar 

  • Dave, C., Caballes, L.: Studies on the uptake of methylglyoxal-bis(guanylhydrazone) and spermidine in mouse leukemia L1210 sensitive and resistant to CH3-G. Fed. Proc. 32, 736 (1973).

    Google Scholar 

  • Dave, C., Mihich, E.: Uptake and intracellular distribution of 4, 4′-diacetyldiphenylurea-bis-(guanylhydrazone) in sensitive and resistant leukemia L1210 cells. Biochem. Pharmacol. 21, 2681–2695 (1972).

    PubMed  CAS  Google Scholar 

  • Dave, C., Ehrke, J., Soucek, J., Mihich, E.: Differences in the action of methylglyoxal-bis-guanylhydrazone, 4, 4,4′-diacetyl-diphenyl-urea-6¿5-guanylhydrazone and related analogs. Fed. Proc. 30, 628 (1971).

    Google Scholar 

  • Davidson, J.R.: Permeability of resistant L1210 leukemia cells to 8-azaguanine and 6-mer-captopurine. Proc. Amer. Ass. Cancer Res. 2, 290 (1958).

    Google Scholar 

  • Dewey, M.M., Barr, L.: Some considerations about the structure of cellular membranes. In: Bonner, F., Kleinzeller, A. (Eds.): Current topics in membrane transport, vol. 1, pp. 1–33. New York: Academic Press 1970.

    Google Scholar 

  • Diamond, I., Kennedy, E.P.: Carrier-mediated transport of choline into synaptic nerve endings. J. biol. Chem. 244, 258–3263 (1969).

    Google Scholar 

  • Divekar, A.Y., Fleysher, M.H., Slocum, H.K., Kenny, L.N., Hakala, M.T.: Changes in Sarcoma 180 cells associated with drug-induced resistance to adenosine analogs. Cancer Res. 32, 2530–2537 (1972).

    PubMed  CAS  Google Scholar 

  • Divekar, A.Y., Vaidya, N.R., Braganca, B.M.: Active transport of aminopterin in Yoshida sarcoma cells. Biochim. biophys. Acta (Amst.) 135, 927–936 (1967).

    CAS  Google Scholar 

  • Dourmashkin, R.R., Dougherty, R.M.: Phagocytosis of crystalline particles by cells grown in tissue culture. Exp. Cell Res. 25, 480–484 (1961).

    PubMed  CAS  Google Scholar 

  • DuBuy, H.G., Showacre, J.L.: Selective localization of tetracycline in mitochondria of living cells. Science 133, 196–197 (1961).

    CAS  Google Scholar 

  • Emmelot, P., Bos, C.J.: Studies on plasma membranes. I. Chemical composition and enzyme content of plasma membranes from rat liver. Biochim. biophys. Acta (Amst.) 90, 126–145 (1966).

    Google Scholar 

  • Field, M., Block, J.B., Oliverio, V.T., Rall, D.P.: Cellular accumulation of methylglyoxal-bis-guanylhydrazone in vitro. I. General characteristics of cellular uptake. Cancer Res. 24, 1939–1946 (1964).

    PubMed  CAS  Google Scholar 

  • Fischer, G.A.: Defective transport of amethopterin as a mechanism of resistance to the antimetabolite. Biochem. Pharmacol. 11, 1233–1237 (1962).

    PubMed  CAS  Google Scholar 

  • Folca, P.J., Glascock, R.F., Irvine, W.T.: Studies with tritium-labeled hexoestrol in advanced breast cancer. Comparison of tissue accumulation of hexoestrol with response to bilateral adrenalectomy and oophorectomy. Lancet 2, 796–798 (1961).

    PubMed  CAS  Google Scholar 

  • Gentry, G.A., Morse, P.A., Ives, D.H., Gebert, R., Potter, V.R.: Pyrimidine metabolism in tissue culture cells derived from rat hepatomas. II. Thymidine uptake in suspension cultures derived from Novikoff hepatomas. Cancer Res. 25, 509–516 (1965).

    PubMed  CAS  Google Scholar 

  • Giannopoulos, G., Gorski, J.: Estrogen receptors. Quantitative studies on transfer of estradiol from cytoplasmic to nuclear binding sites. J. biol. Chem. 246, 2524–2529 (1971a).

    PubMed  CAS  Google Scholar 

  • Giannopoulos, G., Gorski, J.: Estrogen-binding protein of the rat uterus. Different molecular forms associated with nuclear uptake of estradiol. J. biol. Chem. 246, 2530–2536 (1971b).

    PubMed  CAS  Google Scholar 

  • Goldenberg, G. J., Vanstone, C.L., Bihler, L.: Transport of nitrogen mustard on the transport carrier for choline in L5178Y lymphoblasts. Science 172, 1148–1149 (1971).

    PubMed  CAS  Google Scholar 

  • Goldenberg, G.J., Vanstone, C.L., Israels, L.G., Ilse, D., Bihler, L.: Evidence for a transport carrier of nitrogen mustard in nitrogen mustard-sensitive and -resistant L5178 Y lymphoblasts. Cancer Ees. 30, 2285–2291 (1970).

    CAS  Google Scholar 

  • Goldman, I.D.: Transport energetics of the folic acid analog, methotrexate, in L1210 leukemia cells. J. biol. Chem. 244, 3779–3785 (1969).

    PubMed  CAS  Google Scholar 

  • Goldman, I.D.: The characteristics of the membrane transport of amethopterin and the naturally occurring folates. Ann. N. Y. Acad. Sci. 186, 400–422 (1971a).

    PubMed  CAS  Google Scholar 

  • Goldman, I.D.: A model system for the study of heteroexchange diffusion: methotrexate- folate interactions in L1210 leukemia and Ehrlich ascites tumor cells. Biochim. biophys. Acta (Amst.) 233, 624–634 (1971b).

    CAS  Google Scholar 

  • Goldman, I.D., Lichtenstein, N.S., Oliverio, V.T.: Carrier transport of the folic acid analogue, methotrexate, in the L1210 leukemia cell. J. biol. Chem. 243, 5007–5017 (1968).

    PubMed  CAS  Google Scholar 

  • Graham, J.M., Green, C.: The binding of hormones and related compounds by normal and cholesterol-depleted plasma membranes of rat liver. Biochem. Pharmacol. 18, 493–502 (1969).

    PubMed  CAS  Google Scholar 

  • Grindey, G., Nichol, C.A.: Interaction of drugs inhibiting different steps in the synthesis of DNA. Cancer Res. 32, 527–531 (1972).

    PubMed  CAS  Google Scholar 

  • Haeala, M.T.: On the role of drug penetration in amethopterin resistance of S-180 cells in vitro. Biochim. biophys. Acta (Amst.) 102, 198–209 (1965a).

    Google Scholar 

  • Hakala, M.T.: On the nature of permeability of S-180 cells to amethopterin in vitro. Biochim. biophys. Acta (Amst.) 102, 210–225 (1965b).

    CAS  Google Scholar 

  • Hakala, M.T.: Biochemical basis of resistance to folic acid antagonists. PEBS Symp. 16, 31–47 (1969).

    Google Scholar 

  • Hakala, M.T.: Uptake and distribution of 4, 4′-diacetyl-diphenyl-urea-bis-guanylhydrazone in sensitive and resistant Sarcoma 180 cells in vitro. Biochem. Pharmacol. 20, 81–95 (1971).

    PubMed  CAS  Google Scholar 

  • Hakala, M.T.: Enzyme changes in resistant tissues. In: Mihich, E. (Ed.): Drug resistance and selectivity: biochemical and cellular basis, pp. 263–298. New York: Academic Press 1973.

    Google Scholar 

  • Hakala, M.T., Chheda, G.B., Kenny, L.N.: Kinetics and specificity of uptake of 8–14C-purine and 2–14C-pyrimidine nucleosides in Sarcoma 180 cells in vitro. Abstracts, Am. Chem. Soc. Meeting, Chicago, August 1973, Biol. No. 233 (1973).

    Google Scholar 

  • Hakala, M.T., Kenny, L.N.: Common mechanism for the passage of purine and pyrimidine nucleosides through the plasma membrane of Sarcoma 180 cells. Fed. Proc. 31, 475 (1972).

    Google Scholar 

  • Hakala, M.T., Kenny, L.N., Slocum, H.K.: Inhibition of adenosine uptake by N 6-(∆ 2-isopentenyl) adenosine and kinetin riboside. Fed. Proc. 30, 697 (1971).

    Google Scholar 

  • Hakala, M.T., Suounna, E.M., Kenny, L.N., Tritsch, G.: Biochim. biophys. Acta (Amst.), in press.

    Google Scholar 

  • Hall, T.C., Roberts, D., Kessel, D.: Methotrexate and folate reductase in human cancer. Europ. J. Cancer 2, 135–142 (1966).

    CAS  Google Scholar 

  • Hamilton, W.A.: The mode of action of membrane-active antibacterials. Fed. Europ. biochem. Soc. 20, 71 (1970).

    Google Scholar 

  • Hansen, P., Stein, H.: On the synthesis of RNA in lymphocytes stimulated by phyto-hemagglutinin. I. Induction of uridine kinase and the conversion of uridine to UTP. Europ. J. Biochem. 4, 401–406 (1968).

    Google Scholar 

  • Harvey, A.M., Christensen, H.N.: Uric acid transport system. Apparent absence in erythrocytes of the Dalmatian coach hound. Science 145, 826–827 (1964).

    PubMed  CAS  Google Scholar 

  • Hawkins, R.A., Berlin, R.D.: Purine transport in polymorphonuclear leukocytes. Biochim. biophys. Acta (Amst.) 173, 324–337 (1969).

    CAS  Google Scholar 

  • Heidrick, M.L., Ryan, W.L.: Cyclic nucleotides on cell growth in vitro. Cancer Res. 30, 376–378 (1970).

    PubMed  CAS  Google Scholar 

  • Henderson, E.S., Adamson, R.H., Oliverio, V.T.: The metabolic fate of tritiated methotrexate. II. Absorption and excretion in man. Cancer Res. 25, 1018–1024 (1965).

    PubMed  CAS  Google Scholar 

  • Ho, Y.K., Hakala, M.T., Zakrzewski, S.F.: 5-(l-Adamantyl)pyrimidines as inhibitors of folate metabolism. Cancer Res. 32, 1023–1028 (1972).

    PubMed  CAS  Google Scholar 

  • Hodgkin, A.L., Martin, K.: Choline uptake by giant axons of Loligo. J. Physiol. (Lond.) 179, 26P–27P (1965).

    CAS  Google Scholar 

  • Hollander, N., Chiu, Y.W.: In vitro binding of Cortisol[1–2-H3] by a substance in the supernatant fraction of P1798 mouse lymphosarcoma. Biochem. biophys. Res. Comm. 25, 291–297 (1966).

    PubMed  CAS  Google Scholar 

  • Holmsen, H., Rozenberg, M.C.: Adenine nucleotide metabolism of blood platelets. I. Adenosine kinase and nucleotide formation from exogenous adenosine and AMP. Biochim. biophys. Acta (Amst.) 155, 326–341 (1968).

    CAS  Google Scholar 

  • Holter, H.: Pinocytosis. Int. Rev. Cytol. 8, 481–504 (1959).

    PubMed  CAS  Google Scholar 

  • Jacquez, J.A.: Permeability of Ehrlich (ascites) cells to uracil, thymine, and fluorouracil. Proc. Soc. exp. Biol. (N.Y.) 109, 132–135 (1962a).

    CAS  Google Scholar 

  • Jacquez, J.A.: Transport and enzymic splitting of pyrimidine nucleosides in Ehrlich cells. Biochim. biophys. Acta (Amst.) 61, 265–277 (1962b).

    CAS  Google Scholar 

  • Jacquez, J.A.: Permeability of Ehrlich ascites cells to folic acid, aminopterin and amethopterin. Cancer Res. 26, 1616–1624 (1966).

    PubMed  CAS  Google Scholar 

  • Jacquez, J.A., Ginsberg, F.: Permeability of Ehrlich ascites cells to adenine. Proc. Soc. exp. Biol. (N. Y.) 105, 478–480 (1960).

    CAS  Google Scholar 

  • Jost, J.P., Rickenberg, H.V.: Cyclic AMP. Ann. Rev. Biochem. 40, 741–774 (1971).

    CAS  Google Scholar 

  • Kessel, D.: A comparison of 4-amino, N 10-methylpteroic acid and methotrexate transport by mouse leukemic cells. Molec. Pharmacol. 5, 21–25 (1969).

    CAS  Google Scholar 

  • Kessel, D., Botterill, V., Hall, T.C.: Stimulation by pteridines of the uptake of amethopterin by human lymphocytes. Biochem. Pharmacol. 17, 1727–1733 (1968a).

    PubMed  CAS  Google Scholar 

  • Kessel, D., Bruns, R., Hall, T.C.: Determinants of responsiveness to 5-fluorouridine in transplantable murine leukemias. Molec. Pharmacol. 7, 117–121 (1971).

    CAS  Google Scholar 

  • Kessel, D., Hall, T.C.: Studies on drug transport by normal human leukocytes. Biochem. Pharmacol. 16, 2395–2403 (1967a).

    PubMed  CAS  Google Scholar 

  • Kessel, D., Hall, T.C.: Amethopterin transport in Ehrlich ascites carcinoma and L1210 cells. Cancer Res. 27, 1539–1543 (1967b).

    PubMed  CAS  Google Scholar 

  • Kessel, D., Hall, T.C.: Effects of persantin on deoxycytidine transport by murine leukemia cells. Biochim. biophys. Acta (Amst.) 211, 88–94 (1970).

    CAS  Google Scholar 

  • Kessel, D., Hall, T.C., Roberts, D.: Modes of uptake of methotrexate by normal and leukemic human leukocytes in vitro and their relation to drug response. Cancer Res. 28, 564–570 (1968b).

    PubMed  CAS  Google Scholar 

  • Kessel, D., Hall, T.C., Roberts, D., Wodinsky, I.: Uptake as a determinant of amethopterin response in mouse leukemias. Science 150, 752–754 (1965).

    PubMed  CAS  Google Scholar 

  • Kessel, D., Myers, M., Wodinsky, I.: Accumulation of two alkylating agents, nitrogen mustard and busulfan, by murine leukemia cells in vitro. Biochem. Pharmacol. 18, 1229–1234 (1969).

    PubMed  CAS  Google Scholar 

  • Kessel, D., Shurin, S.B.: Transport of two non-metabolizable nucleosides, deoxycytidine and arabinosylcytosine in a subline of L1210 murine leukemia. Biochim. biophys. Acta (Amst.) 163, 179–187 (1968).

    CAS  Google Scholar 

  • Kirkpatrick, A.F., Kaiser, N., Milholland, R. J., Rosen, F.: Glucocorticoid-binding macro-molecules in normal tissues and tumors. Stabilization of the specific binding component. J. biol. Chem. 247, 70–74 (1972).

    PubMed  CAS  Google Scholar 

  • Kotyk, A.: Present situation in the identification of membrane transport proteins of single cells. Fed. Europ. biochem. Soc. 20, 99–108 (1970).

    Google Scholar 

  • Kreis, W., Wechter, W.J.: Biological activity of 3′, 5′-cyclic phosphates of l-β-D-arabino-furanosylcytosine (ara-C). Proc. Am. Ass. Cancer Res. 13, 62 (1972).

    Google Scholar 

  • Kübler, W., Bretschneider, H.J.: Kompetitive Hemmung der katalysierten Adenosin-Diffusion als Mechanismus der coronarerweiternden Wirkung eines Pyrimidopyrimidin-Derivates. Arch. ges. Physiol. 280, 141–157 (1964).

    Google Scholar 

  • Lassen, U.V.: Asymmetry of uric acid transport through the human erythrocyte membrane induced by hypoxanthine. Biochim. biophys. Acta (Amst.) 57, 123–129 (1962).

    CAS  Google Scholar 

  • Lassen, U.V.: Hypoxanthine transport in human erythrocytes. Biochim. biophys. Acta (Amst.) 135, 146–154 (1967).

    CAS  Google Scholar 

  • Lassen, U.V., Overgaard-Hansen, K.: Hypoxanthine as inhibitor of uric acid transport in human erythrocytes. Biochim. biophys. Acta (Amst.) 57, 111–117 (1962a).

    CAS  Google Scholar 

  • Lassen, U.V., Overgaard-Hansen, K.: Purine derivatives as inhibitors of uric acid transport into human erythrocytes. Biochim. biophys. Acta (Amst.) 57, 118–122 (1962b).

    CAS  Google Scholar 

  • Leibman, K.C., Heidelberger, C.: The metabolism of 32P-labeled ribonucleotides in tissue slices and cell suspensions. J. biol. Chem. 216, 823–830 (1955).

    PubMed  CAS  Google Scholar 

  • Lichtenstein, N.S., Goldman, I.D.: Riboflavin-methotrexate interactions. Photochemical reaction and competition for transport in the L1210 mouse leukemia cell. Biochem. Pharmacol. 19, 1229–1239 (1970).

    PubMed  CAS  Google Scholar 

  • Linford, J.H., Hryniuk, W., Israels, L.G.: Adsorption to human red blood cells of chlorambucil and other biological alkylating agents. Biochem. Pharmacol. 18, 2723–2735 (1969).

    PubMed  CAS  Google Scholar 

  • Loo, T.L., Wang-Ho, D.H., Blossom, D.H., Shepard, B.J., Frei, E. III: Cellular uptake of purine antimetabolites in vitro. I. Uptake of methylmercaptopurine riboside by human red blood cells. Biochem. Pharmacol. 18, 1711–1725 (1969).

    PubMed  CAS  Google Scholar 

  • Lowy, B.A., Williams, M.K.: Studies on the metabolism of adenosine and adenine in stored and fresh human erythrocytes. Blood 27, 623–628 (1966).

    PubMed  CAS  Google Scholar 

  • Lowy, B.A., Williams, M.K., London, I.M.: Enzymatic deficiencies of purine nucleotide synthesis in the human erythrocytes. J. biol. Chem. 237, 1622–1625 (1962).

    PubMed  CAS  Google Scholar 

  • Lucas, Z.J.: Pyrimidine nucleotide synthesis: Regulatory control during transformation of lymphocytes in vitro. Science 156, 1237–1240 (1967).

    PubMed  CAS  Google Scholar 

  • Maddy, A.H.: The properties of the protein of the plasma membrane of ox erythrocytes. Biochim. biophys. Acta (Amst.) 117, 193–200 (1966).

    CAS  Google Scholar 

  • Martin, K.: Concentrative accumulation of choline by human erythrocytes. J. gen. Physiol. 51, 497–516 (1968).

    PubMed  CAS  Google Scholar 

  • Marzulli, F.N., Callahan, J.F., Brown, D.W.C.: Chemical structure and skin penetrating capacity of a short series of organic phosphates and phosphoric acid. J. invest. Dermatol. 44, 339–344 (1965).

    PubMed  CAS  Google Scholar 

  • McGuire, W.L., Julian, J. A.: Comparison of macromolecular binding of estradiol in hormone-dependent and hormone-independent rat mammary carcinoma. Cancer Res. 31, 1440–1445 (1971).

    PubMed  CAS  Google Scholar 

  • Mobbs, B.G.: The uptake of tritiated estradiol by 9, 10-dimethyl-1, 2-benzanthracene-induced mammary tumors of the rat. J. Endocrinol. 36, 409–414 (1966).

    PubMed  CAS  Google Scholar 

  • Montgomery, J.A., Dixon, G. J., Dulmage, E.A., Thomas, H.J., Brockman, R.W., Skipper, H.E.: Inhibition of 6-mercaptopurine-resistant cancer cells in culture by bis(thioinosine) 5′, 5″-phosphate. Nature (Lond.) 199, 769–772 (1963).

    CAS  Google Scholar 

  • Nahas, A., Nixon, P.F., Bertino, J.R.: Uptake of 5-formyltetrahydrofolate by L1210 mouse leukemia cells and its effect on uptake of methotrexate. Proc. Amer. Assoc. Cancer Res. 10, 64 (1969).

    Google Scholar 

  • Nakata, Y., Bader, J.P.: The uptake of nucleosides by cells in culture. II. Inhibition by 2-mercapto-l-(β-4-pyridethyl)benzimidazole. Biochim. biophys. Acta (Amst.) 190, 250–256 (1969).

    CAS  Google Scholar 

  • Oliver, J.M., Paterson, A.R.P.: Nucleoside transport. I. A mediated process in human erythrocytes. Canad. J. Biochem. 49, 262 (1971).

    CAS  Google Scholar 

  • Overgaard-Hansen, K., Lassen, U.V.: Active transport of uric acid through the human erythrocyte membrane. Nature (Lond.) 184, 553–554 (1959).

    CAS  Google Scholar 

  • Overman, J.R.: Ingestion of latex particles by chicken fibroblasts in tissue culture. Proc. Soc. exp. Biol. Med. 107, 895–900 (1961).

    PubMed  CAS  Google Scholar 

  • Parpart, A.K., Ballentine, R.: Molecular anatomy of red cell membrane. In: Modern trends in physiology and biochemistry. New York: Academic Press 1952.

    Google Scholar 

  • Paterson, A.R.P.: Resistance to 6-mercaptopurine II. The synthesis of thioinosinic acid in a resistant subline of the Ehrlich ascites carcinoma. Canad. J. Biochem. 40, 195–206 (1962).

    PubMed  CAS  Google Scholar 

  • Paterson, A.R.P., Oliver, J.M.: Nucleoside transport II. Inhibition by p-nitrobenzylthio-guanosine and related compounds. Canad. J. Biochem. 49, 271–274 (1971).

    CAS  Google Scholar 

  • Paterson, A.R.P., Simpson, A.I.: Inhibitors of nucleoside metabolism. Canad. J. Biochem. 44, 1423–1433 (1966).

    CAS  Google Scholar 

  • Penniston, J.T., Beckett, L., Bentley, D.L., Hansch, C.: Passive permeation of organic compounds through biological tissue: A nonsteady state theory. Molec. Pharmacol. 5, 333–341 (1969).

    CAS  Google Scholar 

  • Plagemann, P.G.W.: Nucleoside transport by Novikoff rat hepatoma cells growing in suspension culture. Specificity and mechanism of transport reactions and relationship to nucleoside incorporation into nucleic acids. Biochim. biophys. Acta (Amst.) 233, 688–701 (1971).

    CAS  Google Scholar 

  • Plagemann, P.G. W., Roth, M. F.: Permeation as the rate limiting step in the phosphorylation of uridine and choline and their incorporation in macromolecules by Novikoff hepatoma cells. Competitive inhibition by phenethyl alcohol, persantin and adenosine. Biochem. 8, 4782–4789 (1969).

    CAS  Google Scholar 

  • Plagemann, P.G.W., Ward, G.A., Mahy, B.W.J., Korbecki, M.: Relationship between uridine kinase activity and rate of incorporation of uridine into acid soluble pool and into RNA during growth cycle of rat hepatoma cells. J. cell. Physiol. 73, 233–250 (1969).

    PubMed  CAS  Google Scholar 

  • Plunkett, W., Lapi, L., Ortiz, P., Cohen, S.S.: Cellular penetration and metabolism of 9-β-D-arabinofuranosyl adenine 5’-monophosphate (araAMP). Proc. Am. Ass. Cancer Res. 14, 32 (1973).

    Google Scholar 

  • Potter, L.T.: Uptake of choline by nerve endings isolated from the rat cerebral cortex. In: Campbell, P.N. (Ed.): The interaction of drugs and subcellular components in animal cells, p. 293. Boston: Little, Brown and Co. 1968.

    Google Scholar 

  • Puca, G.A., Nola, E., Sica, V., Bresciani, F.: Estrogen-binding proteins of calf uterus. Partial purification and preliminary characterization of two cytoplasmic proteins. Biochemistry 10, 3769–3780 (1971).

    PubMed  CAS  Google Scholar 

  • Roberts, D.W.: Cleavage of folic acid by hydrogen peroxide. Biochim. biophys. Acta (Amst.) 54, 572–574 (1961).

    CAS  Google Scholar 

  • Roll, P.M., Weinfeld, H., Carroll, E., Brown, G.B.: The utilization of nucleotides by the mammal IV. Triply labeled purine nucleotides. J. biol. Chem. 220, 439–454 (1956).

    PubMed  CAS  Google Scholar 

  • Rosenbloom, F.M., Kelley, W.N., Henderson, J.F., Seegmiller, J.E.: Lyon hypothesis and X-linked disease. Lancet 2, 305–306 (1967).

    Google Scholar 

  • Rothblat, G.H., Buchko, M.K., Rritchevsky, D.: Cholesterol uptake by L5178Y cells: Studies with delipidized serum. Biochim. biophys. Acta (Amst.) 164, 327–338 (1968).

    CAS  Google Scholar 

  • Rubin, R.C., Henderson, E.S., Owens, E.S., Rall, D.P.: Uptake of methotrexate-H3 by rabbit kidney slices. Cancer Res. 27, 553–557 (1967).

    PubMed  CAS  Google Scholar 

  • Ryan, W.L., Heidrick, M.L.: Inhibition of cell growth in vitro by adenosine 3′, 5′-monophosphate. Science 162, 1484–1485 (1968).

    PubMed  CAS  Google Scholar 

  • Ryser, H.J.P., Hancock, R.: Histones and basic polyamino acids stimulate the uptake of albumin by tumor cells in culture. Science 150, 501–503 (1965).

    PubMed  CAS  Google Scholar 

  • Sartorelli, A.C., Iannotti, A.L., Booth, B.A., Schneider, F.H., Bertino, J.R., Johns, D.G.: Complex formation with DNA and inhibition of nucleic acid synthesis by methyl-glyoxal bis(guanylhydrazone). Biochim. biophys. Acta (Amst.) 103, 174–176 (1965).

    CAS  Google Scholar 

  • Schanker, L.S., Jeffrey, J.J.: Active transport of foreign pyrimidines across the intestinal epithelium. Nature (Lond.) 190, 727–728 (1961).

    CAS  Google Scholar 

  • Schanker, L.S., Jeffrey, J.J.: Structural specifity of the pyrimidine transport process of the small intestine. Biochem. Pharmacol. 11, 961–966 (1962).

    PubMed  CAS  Google Scholar 

  • Schanker, L.S., Jeffrey, J.J., Tocco, D.J.: Interaction of purines with the pyrimidine transport process of the small intestine. Biochem. Pharmacol. 12, 1047–1053 (1963).

    PubMed  CAS  Google Scholar 

  • Schanker, L.S., Tocco, D.J.: Active transport of some pyrimidines across the rat intestinal epithelium. J. Pharmacol, exp. Ther. 28, 115–121 (1960).

    Google Scholar 

  • Schanker, L.S., Tocco, D. J.: Some characteristics of the pyrimidine transport process of the small intestine. Biochim. biophys. Acta (Amst.) 56, 469–473 (1962).

    CAS  Google Scholar 

  • Schröder, J., Plagemann, P.G.W.: Growth of Novikoff rat hepatoma cells in suspension culture in the presence of adenosine 3′, 5′-cyclic monophosphate. J. Natl. Cancer Inst. 46, 423–429 (1971).

    PubMed  Google Scholar 

  • Schuberth, J., Sundwall, A., Sorbo, B.: Relation between Na+-K+ transport and the up-take of choline by brain slices. Life Sci. 6, 293–295 (1967).

    PubMed  CAS  Google Scholar 

  • Schuberth, J., Sundwall, A., Sörbo, B., Lindell, J.O.: Uptake of choline by mouse brain slices. J. Neurochem. 13, 347–352 (1966).

    CAS  Google Scholar 

  • Singer, S., Litwack, G.: Identity of corticosteroid binder I with the macromolecule binding 3-methyl cholanthrene in liver cytosol in vivo. Cancer Res. 31, 1364–1368 (1971).

    PubMed  CAS  Google Scholar 

  • Sirotnak, F.M., Kurita, S., Hutchison, D.J.: On the nature of a transport alteration determining resistance to amethopterin in the L1210 leukemia. Cancer Res. 28, 75–80 (1968)

    PubMed  CAS  Google Scholar 

  • Smith, C.G., Reineke, L.M., Burch, M.R., Shefner, A.M., Muirhead, E.E.: Studies on up-take of tubercidin by blood cells and its distribution in whole animals. Cancer Res. 30, 69–75 (1970).

    PubMed  CAS  Google Scholar 

  • Song, C.S., Kappas, A., Bodansky, O.: 5′-NucIeotidase of plasma membranes of the rat liver: Studies on subcellular distribution. Ann. N. Y. Acad. Sci. 166, 565–573 (1969).

    PubMed  CAS  Google Scholar 

  • Steggles, A.W., King, R.J.B.: The uptake of [6, 7-3H] oestradiol by estrogen dependent and independent hamster kidney tumors. Eur. J. Cancer 4, 395–401 (1968).

    PubMed  CAS  Google Scholar 

  • Sung, C.P., Johnstone, R.M.: Evidence for active transport of choline in rat kidney cortex slices. Canad. J. Biochem. 43, 1111–1118 (1965).

    CAS  Google Scholar 

  • Suolinna, E.M., Tritsch, G., Hakala, M.T.: Asparagine and glutamine metabolism in Sarcoma 180 cells in vitro. Proc. Amer. Ass. Cancer Res. 12, 29 (1971).

    Google Scholar 

  • Tan, K.B., Mcauslan, B.R.: Inhibition of nucleoside incorporation into Hela cells by streptovaricin. Biochem. biophys. Res. Comm. 42, 230–236 (1971).

    PubMed  CAS  Google Scholar 

  • Vandevoorde, J.P., Hansen, H.J.: Inhibition of J 128 cell culture by 6-mercaptopurine and 9-alkylated derivatives of 6-mercaptopurine. Proc. Amer. Ass. Cancer Res. 8, 70 (1967).

    Google Scholar 

  • Wartiovaara, V., Collander, R.: Permeabilitätstheorien. In: Protoplasmatologia: Handbuch der Protoplasmaforschung, vol. II, C. 8d. Vienna: Springer 1960.

    Google Scholar 

  • Weiss, L., Hakala, M.T.: The anionic nature of Sarcoma 180 cell surfaces, and sensitivity to 4,4′-diacetyl-diphenyl-urea-bis-guanylhydrazone. Cancer Res. 31, 1369–1372 (1971).

    PubMed  CAS  Google Scholar 

  • Werkheiser, W.C.: Specific binding of 4-amino folic acid analogues by folic acid reductase. J. biol. Chem. 236, 888–893 (1961).

    CAS  Google Scholar 

  • Wilson, T.H., Wdlson, D.W.: Intestinal absorption in vitro of uridylic and thymidylic acids. Biochim. biophys. Acta (Amst.) 22, 587 (1956)

    CAS  Google Scholar 

  • Wilson, T.H., Wdlson, D.W.: Intestinal absorption in vitro of uridylic and thymidylic acids. J. Physiol. 123, 116 (1954).

    PubMed  CAS  Google Scholar 

  • Wilson, T.H., Wilson, D.W.: Studies in vitro of digestion and absorption of pyrimidine nucleotides by the intestine. J. biol. Chem. 233, 1544–1547 (1958).

    PubMed  CAS  Google Scholar 

  • Wolpert, M.K., Ruddon, R. W.: A study on the mechanism of resistance to nitrogen mustard (HN2) in Ehrlich ascites tumor cells: Comparison of uptake of HN2-14C into sensitive and resistant cells. Cancer Res. 29, 873–879 (1969).

    PubMed  CAS  Google Scholar 

  • Yamada, T., Iwanami, Y., Baba, T.: The transport of 14C-labeled nitrogen mustard N-oxide through cellular membrane treated with Tween-80 in vitro. Garni 54, 171–176 (1963).

    CAS  Google Scholar 

  • Yesair, D.W., Kohner, F.A., Rogers, W.I., Baronowsky, P.E., Kensler, C.J.: Relationship of phthalanilide-lipid complexes to uptake and retention of 2-chloro-4′, 4″-di(2-imidazolin-2-yl)terephthalanilide (NSC 60339) by sensitive and resistant P388 leukemia cells. Cancer Res. 26, 202–207 (1966).

    PubMed  CAS  Google Scholar 

  • Yesair, D.W., Rogers, W.I., Baronowsky, P.E., Wodinsky, I., Thayer, P.S., Kensler, C.J.: Relationship of uptake and binding of an antileukemic phthalanilide to its biochemical and chemotherapeutic effects on P388 lymphocytic leukemia cells. Cancer Res. 27, 314–321 (1967).

    PubMed  CAS  Google Scholar 

  • Zakrzewski, S.F.: The mechanism of binding of folate analogues by folate reductase. J. biol. Chem. 238, 1485–1490 (1963a).

    PubMed  CAS  Google Scholar 

  • Zakrzewski, S.F.: Relationship between basicity of certain folate analogues and their affinities for folate reductase. J. biol. Chem. 238, 4002–4004 (1963b).

    PubMed  CAS  Google Scholar 

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  1. M. T. Hakala
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Editors and Affiliations

  1. Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    Alan C. Sartorelli (Professor) (Professor)

  2. Laboratory of Chemical Pharmacology, National Cancer Institute, National Istitutes of Health, Bethesda, Maryland, 20014, USA

    David G. Johns M. D.

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Hakala, M.T. (1974). Transport of Antineoplastic Agents. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents Part I. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65678-1_13

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