Skip to main content
SpringerLink
Log in

Biochemical Aspects of Selective Toxicity

  • Chapter
Book cover Antineoplastic and Immunosuppressive Agents Part I

Abstract

Selective toxicity, i.e. differences in the biological consequences of drug action on normal and neoplastic cells, is the very basis of cancer chemotherapy, and the increasing effectiveness of drugs for the treatment of childhood leukemia, Burkitt’s lymphoma, choriocarcinoma, and some other types of neoplastic disease, demonstrates that such selectivity can be achieved even in man. However, the large number of patients who still die of malignant disease testify that selectivity of drug action is not attained with sufficient frequency or reliability.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ball, C.R., Roberts, J.: DNA repair after mustard gas alkylation by sensitive and resistant Yoshida sarcoma cells in vitro. Chem. Biol. Interact. 2 321–329 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Bertino, J.R., Hillcoat, B.L.: Regulation of dihydrofolate reductase and other folate-requiring enzymes. Adv. Enzyme Regulat. 6 335–349 (1968).

    Article  CAS  Google Scholar 

  • Brockman, R.W.: Resistance to purine antagonists in experimental leukemia systems. Cancer Res. 25 1596–1605 (1965).

    PubMed  CAS  Google Scholar 

  • Chun, E.H.L., Gonzales, L., Lewis, F.S., Jones, J., Rutman, R. J.: Differences in the in vivo alkylation and cross-linking of nitrogen mustard-sensitive and -resistant lines of Leuré- Ehrlich ascites tumors. Cancer Res. 29 1184–1194 (1969).

    PubMed  CAS  Google Scholar 

  • Farber, E.: Biochemical pathology. Ann. Rev. Pharmacol. 11 71–96 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Farber, E., Baserga, R.: Differential effects of hydroxyurea on survival of proliferating cells in vivo. Cancer Res. 29 136–139 (1969).

    PubMed  CAS  Google Scholar 

  • Fernandes, J.F., LePage, G. A., Lindner, A.: The influence of azaserine and 6-mercaptopurine on the in vivo metabolism of ascites tumor cells. Cancer Res. 16 154–161 (1956).

    PubMed  CAS  Google Scholar 

  • Fisoher, G.A.: Defective transport of amethopterin as a mechanism of resistance to the antimetabolite in L5178Y leukemic cells. Biochem. Pharmacol. 11 1233–1234 (1962).

    Article  Google Scholar 

  • Gellhorn, A.: Laboratory and clinical studies on 8-azaguanosine. Cancer 6 1030–1033 (1953).

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Guillino, P.M., Grantham, F.H., Smith, S.H., Haggerty, A.C.: Modifications of the acid-base status of the internal milieu of tumors. J. nat. Cancer Inst. 34 857–869 (1965).

    Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Heidelberger, C., Kaldor, G., Mukherjee, K.L., Danneberg, P.B.: Studies on fluorinated pyrimidines. XI. In vitro studies on tumor resistance. Cancer Res. 20 903–909 (1960).

    PubMed  CAS  Google Scholar 

  • Henderson, J.F.: Variation in selective toxicity: Causes and consequences. Cancer Res. 29, 2404–2406 (1969).

    PubMed  CAS  Google Scholar 

  • Henderson, J.F., Caldwell, I.C., Paterson, A.R.P.: Decreased feedback inhibition in a 6-(methylmercapto)purine ribonucleoside-resistant tumor. Cancer Res. 27 1773–1778 (1967).

    PubMed  CAS  Google Scholar 

  • Henderson, J.F., LePage, G.A., McIver, F.A.: Observations on the action of azaserine in mammalian tissues. Cancer Res. 17 609–612 (1957).

    PubMed  CAS  Google Scholar 

  • Hennings, H., Devik, F.: Comparison of cytotoxicity of hydroxyurea in normal and rapidly proliferating epidermic and small intestine in mice. Cancer Res. 31 277–282 (1971).

    PubMed  CAS  Google Scholar 

  • Hirschberg, E., Kream, J., Gellhorn, A.: Enzymatic deamination of 8-azaguanine in normal and neoplastic tissues. Cancer Res. 12 524–528 (1952).

    PubMed  CAS  Google Scholar 

  • Ho, D.H.W., Luce, J.K., Frei, E.: Distribution of purine ribonucleoside kinase and selective toxicity of 6-methylthiopurine ribonucleoside. Biochem. Pharmacol. 17 1025–1035 (1968).

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Jacquez, J.A., Sherman, J.H.: Enzymatic degradation of azaserine. Cancer Res. 22 56–61 (1962).

    PubMed  Google Scholar 

  • Kahler, H., Robertson, W.B.: Hydrogen-ion concentration of normal liver and hepatic tumors. J. nat. Cancer Inst. 3 495–501 (1943).

    CAS  Google Scholar 

  • Kessel, D., Hall, T.C.: Uptake and efflux of tritiated methotrexate by leukocytes. Clin. Res. 13 338 (1965).

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kessel, D., Hall, T.C.: Retention of 6-mercaptopurine derivatives by intact cells as an index of drug response in human and murine leukemias. Cancer Res. 29 2116–2119 (1969).

    PubMed  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 (1968).

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kessel, D., Hall, T.C., Rosenthal, D.: Uptake and phosphorylation of cytosine arabinoside by normal and leukemic human blood cells in vitro. Cancer Res. 29 459–463 (1969).

    PubMed  CAS  Google Scholar 

  • Klau, O., Stehlin, J.S., Jr., Mcbride, C., Griffin, A.C.: The effect of nitrogen mustard treatment on the deoxyribonucleic acid of sensitive and resistant Ehrlich tumor cells. Cancer Res. 29 286–290 (1969).

    Google Scholar 

  • Kreis, W., Drahovsky, D., Borberg, H.: Characterization of protein and DNA in P815 cells sensitive and resistant to 1-β-D-arabinofuranosylcytosine. Cancer Res. 32 696–701 (1972).

    PubMed  CAS  Google Scholar 

  • Krenitsky, T.A.: Tissue distribution of purine ribosyl- and phosphoribosyltransferases in the Rhesus monkey. Biochim. biophys. Acta (Amst.) 179 506–509 (1969).

    CAS  Google Scholar 

  • LePage, G.A.: Alterations in enzyme activity in tumors and the implications for chemotherapy. Adv. Enzyme Regulat. 8 323–332 (1970).

    Article  CAS  Google Scholar 

  • Lieberman, M.W., Verbin, R.S., Landay, M., Liang, H., Farber, E., Lee, T.N., Starr, R.: A probable role for protein synthesis in intestinal epithelial cell damage induced in vivo by cytosine arabinoside, nitrogen mustard, or x-irradiation. Cancer Res. 30 942–951 (1970).

    PubMed  CAS  Google Scholar 

  • Lyons, R.M., Goldenberg, G.J.: Active transport of nitrogen mustard by normal and leukemic human lymphoid cells. Proc. Amer. Ass. Cancer Res. 13 15 (1972).

    Google Scholar 

  • Marchesi, S.L., Sartorelli, A.C.: The biochemical basis for the differential sensitivity of intestinal mucosa and bone marrow to 6-thioguanine. Cancer Res. 23 1769–1773 (1963).

    PubMed  CAS  Google Scholar 

  • Moore, E.C., LePage, G.A.: In vivo sensitivity of normal and neoplastic mouse tissue to azaserine. Cancer Res. 17 804–808 (1957).

    PubMed  CAS  Google Scholar 

  • Moore, E.C., LePage, G.A.: The metabolism of 6-thioguanine in normal and neoplastic tissues. Cancer Res. 18 1075–1083 (1958).

    PubMed  CAS  Google Scholar 

  • Murray, A.W.: Purine-phosphoribosyltransferase activities in rat and mouse tissues and in Ehrlich ascites-tumor cells. Biochem. J. 100 664–670 (1966).

    PubMed  CAS  Google Scholar 

  • Nichol, C.A.: Studies on dihydrofolate reductase related to the drug sensitivity of microbial and neoplastic cells. Adv. Enzyme Regulat. 6 305–322 (1968).

    Article  CAS  Google Scholar 

  • Oliver, J.M., Paterson, A.R.P.: Nucleoside transport I. A mediated process in human erythrocytes. Canad. J. Biochem. 49 262–270 (1971).

    Article  CAS  Google Scholar 

  • Peery, A., LePage, G.A.: Nucleotide formation from α and β-2′-deoxythioguanosine in extracts of murine and human tissues. Cancer Res. 29, 617–623 (1969).

    PubMed  CAS  Google Scholar 

  • Pfeiffer, S.E., Tolmach, L. J.: Inhibition of DNA synthesis in HeLa cells by hydroxyurea. Cancer Res. 27 124–129 (1967).

    PubMed  CAS  Google Scholar 

  • Philips, F.S., Sternberg, S.S., Schwartz, H.S., Cronin, A.P., Sodergren, J.E., Vidal, P.M.: Hydroxyurea. I. Acute cell death in proliferating tissues in rats. Cancer Res. 27 61–74 (1967).

    PubMed  CAS  Google Scholar 

  • Poole, D.T., Butler, T. C., Waddell, W.J.: Intracellular pH of the Ehrlich ascites tumor cell. J. nat. Cancer Inst. 32 939–946 (1964).

    CAS  Google Scholar 

  • Rall, D.P.: Selective aspects of chemotherapy in acute leukemia and Burkiu’s tumor. Cancer 21 575–579 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Roberts, D., Hall, T.C.: The reduction of folate and dihydrofolate by homogenates of leukocytes from patients with leukemia or with myeloid metaplasia. Cancer Res. 27 994–999 (1967).

    PubMed  CAS  Google Scholar 

  • Roberts, J.J., Crathorn, A.R., Brent, T.P.: Repair of alkylated DNA in mammalian cells. Nature (Lond.) 218 970–972 (1968).

    Article  CAS  Google Scholar 

  • Rosenbloom, F.M., Kelley, W.N., Miller, J., Henderson, J.F., Seegmiller, J.E.: Inherited disorder of purine metabolism. Correlation between central nervous system dysfunction and biochemical effects. J. Amer. med. Assoc. 202 175–177 (1967).

    Article  CAS  Google Scholar 

  • Rutman, R.J., Chun, E.H.L., Lewis, F.S.: Permeability difference as a source of resistance to alkylating agents in Ehrlich ascites tumor cells. Biochem. biophys. Res. Commun. 32 650–657 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Sartorelli, A.C.: Some approaches to the therapeutic exploitation of metabolic sites of vulnerability of neoplastic cells. Cancer Res. 29 2292–2299 (1969).

    PubMed  CAS  Google Scholar 

  • Sartorelli, A.C., LePage, G.A.: The development and biochemical characterization of resistance to azaserine in a TA3 ascites carcinoma. Cancer Res. 18 457–463 (1958).

    PubMed  CAS  Google Scholar 

  • Schwartz, H.S., Garofalo, M., Sternberg, S.S., Philips, F.S.: Hydroxyurea: Inhibition of deoxyribonucleic acid synthesis in regenerating liver of rats. Cancer Res. 25 1867–1870 (1965).

    PubMed  CAS  Google Scholar 

  • Sinclair, W.K.: Hydroxyurea: Effects on Chinese hamster cells grown in culture. Cancer Res. 27 297–308 (1967).

    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 

  • Skipper, H.E.: The cell cycle and chemotherapy of cancer. In: The cell cycle and cancer. New York: Marcel Dekker 1971.

    Google Scholar 

  • Sneider, T.W., Pouer, V.R.: Alternative de novo and “salvage” pathways to thymidine triphosphate synthesis: Possible implications for cancer chemotherapy. Cancer Res. 29 2398–2403 (1969).

    PubMed  CAS  Google Scholar 

  • Walker, I. G., Reid, B. D.: Some properties of substrains of L-cells with a decreased sensitivity to bis(2-chloroethyl)sulfide. Cancer Res. 31 510–515 (1971).

    PubMed  CAS  Google Scholar 

  • Werkheiser, W.C., Law, L.W., Roosa, R.A., Nichol, C.A.: Further evidence that selective uptake modifies cellular response to 4-aminofolate antagonists. Proc. Amer. Ass. Cancer Res. 4 71 (1963).

    Google Scholar 

  • Wolpert, M.K., Damle, S.R, Brown, J.E., Sznycer, E., Agrawal, K.C., Sartorelli, A.C: The role of phosphohydrolases in the mechanism of resistance of neoplastic cells to 6-thiopurines. Cancer Res. 31 1620–1626 (1971).

    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 

  • Young, C.W., Schochetman, G., Karnopsky, D. A.: Hydroxyurea-induced inhibition of deoxyribonucleotide synthesis: Studies in intact cells. Cancer Res. 27 526–534 (1967).

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. J. Frank Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

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.

Rights and permissions

Reprints and permissions

Copyright information

© 1974 Springer-Verlag Berlin · Heidelberg

About this chapter

Cite this chapter

Henderson, J.F. (1974). Biochemical Aspects of Selective Toxicity. 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_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-65678-1_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-65680-4

  • Online ISBN: 978-3-642-65678-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation