Skip to main content
SpringerLink
Log in

Site of Action of Cytotoxic Agents in the Cell Life Cycle

  • Chapter
Antineoplastic and Immunosuppressive Agents Part I

Abstract

In the past decade a considerable interest in the mechanisms of action of cytotoxic agents at the cellular level has been generated. The work of Bruce (1966) and his collaborators (Bruce et al., 1966, 1969) comparing rapidly dividing transplantable murine lymphoma cells with essentially “resting” normal bone marrow cells, both of which form colonies in the spleen, showed that some lethal agents may be regarded as cell cycle specific, or even phase specific within the cycle, while others act on resting noncycling cells to the same extent as on cycling cells. This in vivo work was augmented by the demonstration in vitro that cells in the “stationary phase” of the growth cycle may be relatively inert to some of the agents which act preferentially on proliferating exponential phase cultured cells (Bhuyan et al., 1962; Madoc-Jones and Bruce, 1967; Hahn, 1969; Hryniuk et al., 1969; Borsa and Whitmore, 1969). The obvious application of this type of work to the problem of designing treatment schedules for malignant disease (vide Schabel et al., 1965; Baserga, 1965; Skipper et al., 1967; Schabel, 1968; for example) spurred much research towards defining which agents exert their lethal effect at which phase of the cell generation cycle, that is in G 1, S, G 2, or M as defined in previous chapters of this volume.

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

  • Bacchetti, S., Sinclaib, W.K.: The relation of protein synthesis to radiation-induced division delay in Chinese hamster cells. Eadiat. Res. 44, 788–806 (1970).

    CAS  Google Scholar 

  • Bacchetti, S., Whitmobb, G.F.: Actinomycin D and X-ray sensitivity in synchronized mouse L-cells. Radiat. Res. 81, 577–578 (1967).

    Google Scholar 

  • Bacchetti, S., Whitmore, G.F.: The action of hydroxyurea on mouse L-cells. Cell Tissue Kinet. 2, 193–211 (1969a).

    CAS  Google Scholar 

  • Bacchetti, S., Whitmore, G.F.: Actinomycin D: Effects on mouse L-cells. Biophys. J. 9, 1427–1455 (1969b).

    PubMed  CAS  Google Scholar 

  • Balis, M.E., Danois, J.: Effects of amethopterin on nucleic acid synthesis in leukemic spleen breis. Cancer Res. 15, 603–608 (1955).

    PubMed  CAS  Google Scholar 

  • Barranco, S.C., Humphrey,R.M.: The effects of l, 3–bis(2-chloroethyl)-l-nitrosourea on survival and cell progression in Chinese hamster cells. Cancer Res. 31, 191–195 (1971a).

    PubMed  CAS  Google Scholar 

  • Barranco, S.C.,Humphrey, R.M.: The effects of bleomycin on survival and cell progression in Chinese hamster cells in vitro. Cancer Res. 31, 1218–1223 (1971b).

    PubMed  CAS  Google Scholar 

  • Baserga, R.: The relationship of the cell cycle to tumor growth and control of cell division: A review. Cancer Res. 25, 581–595 (1965).

    PubMed  CAS  Google Scholar 

  • Baserga, R.,Estensen, R.D., Petersen,R. O.: Inhibition of DNA synthesis in Ehrlich ascites cells by actinomycin D, II. The presynthetic block in the cell cycle. Proc. nat. Acad. Sci. (Wash.) 54, 1141–1148 (1965).

    CAS  Google Scholar 

  • Bhuyan,B.K., Reuis, H.E., Smith, C.G.: A collagen plate assay for cytotoxic agents. II. Biological studies. Cancer Res. 22, 1131–1136 (1962).

    PubMed  CAS  Google Scholar 

  • Bhuyan, B.K., Scheldt, L.G., Fraser, T. J.: Cell cycle phase specificity of antitumor agents. Cancer Res. 32, 398–407 (1972).

    PubMed  CAS  Google Scholar 

  • Borsa, J., Whitmore, G.F.: Cell killing studies on the mode of action of methotrexate on L-cells in vitro. Cancer Res. 29, 737–744 (1969).

    PubMed  CAS  Google Scholar 

  • Bremerskov, V., Kaden, P., Mittermayer, C.: DNA synthesis during the life cycle of L-cells: Morphological, histochemical and biochemical investigations with arabinosyl-cytosine and thioarabinosylcytosine. Europ. J. Cancer 6, 379–392 (1970).

    CAS  Google Scholar 

  • Brubaker, P.E., Flamm, W.G., Beruhelm, W.J.: Effect of γ-chlordane on synchronized lymphoma cells and inhibition of cell division. Nature (Lond.) 226, 548–549 (1970).

    CAS  Google Scholar 

  • Bruchovsky, N., Owen, A.A., Becker, A.J., Till, J.E.: Effects of vinblastine on the pro-liferative capacity of L-cells and their progression through the division cycle. Cancer Res. 25, 1232–1237 (1965).

    PubMed  CAS  Google Scholar 

  • Bruce, W.R.: The action of chemotherapeutic agents at the cellular level and the effects of these agents on hematopoietic and lymphomatous tissue. Can. Cancer Conf. 7, 53–64 (1966).

    CAS  Google Scholar 

  • Bruce, W.R., Meeker, B.E., Valeriote, F.A.: Comparison of the sensitivity of normal hematopoietic and transplanted lymphoma colony-forming cells to chemotherapeutic agents administered in vivo. J. nat. Cancer Inst. 37, 233–245 (1966).

    PubMed  CAS  Google Scholar 

  • Bruce, W.R., Meeker, B.E., Powers, W.E., Valeriote, F.A.: Comparison of the dose- and time-survival curves for normal hematopoietic and lymphoma colony-forming cells exposed to vinblastine, vincristine, arabinosylcytosine, and amethopterin. J. nat. Cancer Inst. 42, 1015–1023 (1969).

    PubMed  CAS  Google Scholar 

  • Burchenal, J.H., Babcock, G.M.: Prevention of toxicity of massive doses of A-methopterin by citrovorum factor. Proc. Soc. exp. Biol. (N. Y.) 76, 382–384 (1951).

    CAS  Google Scholar 

  • Cardinali, G., Mehrota, T.N.: Comparative studies on the stathmokinetic effect of vincristine (VCR), vinblastine (VLB), and colchicine. Proc. Amer. Assoc. Cancer Res. 4, 10–11 (1963).

    Google Scholar 

  • Caspersson, T., Faber, S., Foley, G.E., Killander, D.: Cytochemical observations on the nucleolus-ribosome system: Effects of actinomycin D and nitrogen mustard. Exp. cell Res. 32, 529–552 (1963).

    PubMed  CAS  Google Scholar 

  • Cline, M.J.: Effect of vincristine on synthesis of ribonucleic acid and protein in leukemic leukocytes. Brit. J. Haemat. 14, 21–29 (1968).

    PubMed  CAS  Google Scholar 

  • Creasey, W.A., Markiw, M.E.: Biochemical effects of the Vinca alkaloids, II. A comparison of the effects of colchicine, vinblastine and vincristine on the synthesis of ribonucleic acid in Ehrlich ascites carcinoma cells. Biochim. Biophys. Acta (Amst.) 87, 601–609 (1964).

    CAS  Google Scholar 

  • Cutts, J.H.: The effect of vincaleukoblastine on dividing cells in vivo. Cancer Res. 21, 168–172 (1961).

    PubMed  CAS  Google Scholar 

  • Demars, R.L., Hooper, J.L.: A method for selecting for auxotrophic mutants of Hela cells. J. exp. Med. 111, 559–572 (1960).

    CAS  Google Scholar 

  • Djordjevic, B., Kim, J.H.: Lethal effect of phleomycin in different stages of the division cycle of Hela cells. Cancer Res. 27, 2255–2261 (1967).

    PubMed  CAS  Google Scholar 

  • Djordjevic, B., Kim, J.H.: Different lethal effects of mitomycin C and actinomycin D during the division cycle of Hela cells. J. cell Biol. 38, 477–483 (1968).

    PubMed  CAS  Google Scholar 

  • Djordjevic, B., Tolmach, L. J.: Responses of synchronous populations of Hela cells to ultra-violet irradiation at selected stages of the generation cycle. Biophys. J. 32, 327–347 (1967).

    CAS  Google Scholar 

  • Doi, O., Takai, S., Aoki, Y., Higashi,H., Kosaki, G.: Effects of mitomycin C on Hela cells at various stages of the division cycle. Gann 58, 125–127 (1967).

    PubMed  CAS  Google Scholar 

  • Domon, M., Kauth, A.: Ultraviolet irradiation of mouse L-cells: Effects of DNA synthesis and progression through the cell cycle. Radiat. Res. 35, 350–368 (1968).

    PubMed  CAS  Google Scholar 

  • Dustin, P.: New aspects of the pharmacology of antimitotic agents. Pharmacol. Rev. 15, 449–480 (1963).

    PubMed  CAS  Google Scholar 

  • Elkind, M.M., Kano, E.: Actinomycin D and radiation fractionation studies in asynchronous and synchronized Chinese hamster cells. Radiat. Res. 44, 484–497 (1970).

    PubMed  CAS  Google Scholar 

  • Elkind, M.M., Whitmore, G.F.: The radiobiology of cultured mammalian cells, Chapter 7. New York: Gordon & Breach 1967.

    Google Scholar 

  • Elkind, M.M., Sakamoto, K., Kamper, C.: Age-dependent toxic properties of actinomycin D and X-rays in cultured Chinese hamster cells. Cell Tissue Kinet. 1, 209–224 (1968).

    CAS  Google Scholar 

  • Epifanova, O.I., Smolenskaya, I.N., Sevestyanova, M.V., Kurdyumova, A.G.: Effect of actinomycin D and puromycin on the mitotic cycle in synchronized cell cultures. Exp. cell Res. 58, 401–410 (1969).

    PubMed  CAS  Google Scholar 

  • Fox, M., Fox, B.W.: Effect of methyl methanesulfonate on the growth of P388 lymphoma cells in vitro and on their rate of progress through the cell cycle. Cancer Res. 27, 1805–1812 (1967).

    PubMed  CAS  Google Scholar 

  • Fujiwara, Y.: Role of RNA synthesis in DNA duplication of synchronized populations of cultured mammalian cells. J. cell. comp. Physiol. 70, 291–300 (1967).

    CAS  Google Scholar 

  • Gelfant, S.: Inhibition of cell division. A critical and experimental analysis. Int. Rev. Cytol. 14, 1–39 (1963).

    PubMed  CAS  Google Scholar 

  • Gillette, E.L., Withers, H.R., Tannock, I.F.: The age sensitivity of epithelial cells of mouse small intestine. Radiology 96, 639–643 (1970).

    PubMed  CAS  Google Scholar 

  • Hahn, G.H.: Radiochemotherapy of cell cultures containing cycling and non-cycling cells. Front. Radiation Ther. One. 4, 17–23 (1969).

    Google Scholar 

  • Han, A., Sinclair, W.K.: Sensitivity of synchronized Chinese hamster cells to ultraviolet light. Biophys. J. 9, 1171–1192 (1969).

    PubMed  CAS  Google Scholar 

  • Hryniuk, W.M., Fisher, G. A., Bertino, J.R.: S-phase cells of rapidly growing and resting populations: Differences in response to methotrexate. Molec. Pharmacol. 5, 557–564 (1969).

    CAS  Google Scholar 

  • Karon, M., Shirakawa, S.: Effect of 1-beta-D-arabinofuranosylcytosine on cell cycle passage time. J. nat. Cancer Inst. 45, 861–867 (1970).

    PubMed  CAS  Google Scholar 

  • Kim, J.H., Gelbard, A.S., Perez, A.G.: Action of hydroxyurea on the nucleic acid metabolism and viability of Hela cells. Cancer Res. 27, 1301–1305 (1967).

    PubMed  CAS  Google Scholar 

  • Klm, J.H., Gelbard, A.S., Djordjevic, B., Kim, S.H., Perez, A.G.: Action of daunomycin on the nucleic acid metabolism and viability of Hela cells. Cancer Res. 28, 2437–2442 (1968).

    Google Scholar 

  • Kim, S.H., Kim, J.H.: Lethal effect of adriamycin on the division cycle of Hela cells. Cancer Res. 32, 323–325 (1972).

    PubMed  CAS  Google Scholar 

  • Kishimoto, S., Liberman, L: Synthesis of RNA and protein required for the mitosis of mammalian cells. Exp. cell Res. 36, 92–101 (1964).

    PubMed  CAS  Google Scholar 

  • Kunimoto, T., Hori, M., Umezawa, H.: Modes of action of phleomycin, bleomycin and formycin on Hela S3 cells in synchronized culture. J. Antibiotics (Tokyo) 20, 277–281 (1967).

    CAS  Google Scholar 

  • Li, L.H., Olin, E.S., Fraser, T.S., Bhuyan, B.K.: Phase specificity of 5-azacytidine against mammalian cells in tissue culture. Cancer Res. 30, 2770–2775 (1970).

    PubMed  CAS  Google Scholar 

  • Littlefield, J.W.: DNA synthesis in partially synchronized l cells. Exp. cell Res. 26, 318–323 (1962).

    PubMed  CAS  Google Scholar 

  • Lozzio, C.B.: Lethal effects of fluorodeoxyuridine on cultured mammalian cells at various stages of the cell cycle. J. cell Physiol. 74, 57–62 (1969).

    PubMed  CAS  Google Scholar 

  • Ludford, R.J.: The action of toxic substances upon the division of normal and malignant cells in vitro and in vivo. Arch. Exp. Zeilforsch. 18, 411–441 (1936).

    CAS  Google Scholar 

  • Madoc-Jones, H., Bruce, W.R.: Comparison of the sensitivity of L cells in exponential and stationary phase to 5-fluorouracil. Nature (Lond.) 215, 302–303 (1967).

    CAS  Google Scholar 

  • Madoc-Jones, H., Mauro, F.: Interphase action of vinblastine and vincristine; Differences in their lethal action through the mitotic cycle of cultured mammalian cells. J. cell Physiol. 72, 185–196 (1968).

    PubMed  CAS  Google Scholar 

  • Madoc-Jones, H., Mauro, F.: Age-responses to x-rays, Vinca alkaloids, and hydroxyurea of murine lymphoma cells synchronized in vivo. J. nat. Cancer Inst. 45, 1131–1143 (1970).

    PubMed  CAS  Google Scholar 

  • Malawista, S.E., Sato, H., Bensch, K.G.: Vinblastine and griseofulvin reversibly disrupt the living mitotic spindle. Science 160, 770–772 (1968).

    PubMed  CAS  Google Scholar 

  • Mauro, F., Elkind, M.M.: Differences in survival variations during the growth cycle of cultured Chinese hamster cells treated with X-rays and sulfur mustard. Cancer Res. 28, 1150–1155 (1968).

    PubMed  CAS  Google Scholar 

  • Mauro, F., Elkind, M.M., Sakamoto, K.: Comparison of survival kinetics and modifications of lethal damage in cultured Chinese hamster cells exposed to sulfur mustard and X-rays. Cancer Res. 28, 1143–1149 (1968).

    PubMed  CAS  Google Scholar 

  • Mauro, F., Madoc-Jones, H.: Age-response to X-irradiation of murine lymphoma cells synchronized in vivo. Proc. nat. Acad. Sci. U.S. 63, 666–691 (1969).

    Google Scholar 

  • Mauro, F., Madoc-Jones, H.: Age-responses of cultured mammalian cells to cytotoxic drugs. Cancer Res. 30, 1397–1408 (1970).

    PubMed  CAS  Google Scholar 

  • Mendelsohn, M.L., Dethlefsen,L.A.: Cell kinetics of breast cancer: The turnover of nonproliferating cells. In: Griem, M.L., Jensen, E.V., Ultmann, J.E., Wissler, R.W.(Eds.): Breast Cancer: a challenging problem. Recent results in cancer research. Berlin-Heidelberg-New York: Springer (in press.).

    Google Scholar 

  • Muchison, J.M.: Enzyme synthesis in synchronous cultures. Science 165, 657–663 (1969).

    Google Scholar 

  • Mueller, G.C., Kajiwara, K.: Actinomycin D and p-fluorophenylalanine inhibition of nuclear replication in Hela cells. Biochim. biophys. Acta (Amst.) 119, 557–565 (1966).

    CAS  Google Scholar 

  • Nias, A.H.W., Fox, M., Fox, B.W.: Kinetics of a drug sensitive clone of Hela cells. Cell Tissue Kinet. 3, 207–215 (1970).

    PubMed  CAS  Google Scholar 

  • Nichol, C.A., Welch, A.D.: On the mechanism of action of aminopterin. Proc. Soc. exp. Biol. (N. Y.) 74, 403–411 (1950).

    CAS  Google Scholar 

  • Nowell, P.C: Mitotic inhibition and chromosome damage by mitomycin in human leukocyte culture. Exp. cell Res. 33. 445–449 (1964).

    PubMed  CAS  Google Scholar 

  • Osborn, M.J., Freeman, M., Huennekens, F.M.: Inhibition of dihydrofolate reductase by aminopterin and amethopterin. Proc. Soc. exp. Biol. (N. Y.) 97, 429–431 (1958).

    CAS  Google Scholar 

  • Palmer, C.G., Livergood, D., Warren, A.K., Simpson, P.J., Johnson, I.S.: The action of vincaleukoblastine on mitosis in vitro. Expt. cell Res. 20, 198–201 (1960).

    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., Lenaz, L.: Susceptibility of intestinal crypt epithelium to hydroxyurea and other antitumor agents. In: Fry, R. J.M., Griem, M.L., Kirsten, W.H. (Eds.): Normal and malignant cell growth. Recent results in cancer research, Vol. 12, pp. 104–108. Berlin-Heidelberg-New York: Springer 1969.

    Google Scholar 

  • Plagemann, P.G.W.: Vinblastine sulfate: Metaphase arrest, inhibition of RNA synthesis, and cytotoxicity, in Novikoff rat hepatoma cells. J. nat. Cancer Inst. 45, 589–595 (1970).

    PubMed  CAS  Google Scholar 

  • Puck, T.T., Marcus, P. I., Cieciura, S.J.: Clonal growth of mammalian cells in vitro. Growth characteristics of colonies of single Hela cells with and without “feeder” layer. J. exp. Med. 103, 273–284 (1956).

    PubMed  CAS  Google Scholar 

  • Rajewsky, M.F.: Synchronization in vivo: Kinetics of a malignant cell system following temporary inhibition of DNA synthesis with hydroxyurea. Exp. cell Res. 60, 269–276 (1970).

    PubMed  CAS  Google Scholar 

  • Rauth, A.M., Whitmore, G.F.: The survival of synchronized L cells after ultraviolet irradiation. Radiat. Res. 28, 84–95 (1966).

    PubMed  CAS  Google Scholar 

  • Roberts, D., Hall, T.C.: Dihydrofolate reductase activity and deoxynucleoside incorporation into DNA of human leukocytes. Cancer 20, 905–910 (1967).

    PubMed  CAS  Google Scholar 

  • Roberts, J.J., Brent, T.P., Crathorn, A.R.: The mechanism of the cytotoxic action of alkylating agents on mammalian cells. In: Campbell, P.N. (Ed.): The interaction of drugs and subcellular components in animal cells, pp. 5–27. Boston: Little, Brown & Co. 1968.

    Google Scholar 

  • Rueckert, R.R., Mueller, G.C.: Studies on unbalanced growth in tissue culture. 1. Induction and consequences of thymidine deficiency. Cancer Res. 20, 1584–1591 (1960).

    PubMed  CAS  Google Scholar 

  • Sakamoto, K., Elkind, M.M.: X-rays and nitrogen mustard: Independent action in Chinese hamster cells. Biophys. J. 9, 1115–1130 (1969).

    PubMed  CAS  Google Scholar 

  • Sartorelli, A.C, LePage, G.A.: Effects of Amethopterin on the purine biosynthesis of susceptible and resistant TA3 ascites cells. Cancer Res. 18, 1336–1339 (1958).

    PubMed  CAS  Google Scholar 

  • Schabel, F.M.: In vivo leukemic cell kill kinetics and “curability” in experimental systems. In: The Proliferation and spread of neoplastic cells, pp. 379–408. Baltimore: Williams & Wilkins 1968.

    Google Scholar 

  • Schabel, F.M., Skipper, H.E., Trader, M.W., Wilcox, W.S.: Experimental evaluation of potential anticancer agents. XIX. Sensitivity of nondividing leukemic cell populations to certain classes of drugs in vivo. Cancer Chemother. Rep. 48, 17–30 (1965).

    PubMed  CAS  Google Scholar 

  • Sharpe, H.B.A., Field, E.O., Hellmann, K.: Mode of action of the cytostatic agent “ICRF 159”. Nature (Lond.) 226, 524–526 (1970).

    CAS  Google Scholar 

  • Sinclant, W.K.: Hydroxyurea: Differential lethal effects on cultured mammalian cells during the cell cycle. Science 150, 1729–1731 (1965).

    Google Scholar 

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

    Google Scholar 

  • Sinclair, W.K.: Cyclic X-ray responses in mammalian cells in vitro. Radiat. Res. 33, 620–643 (1968).

    PubMed  CAS  Google Scholar 

  • Sinclair, W.K.: Methods and criteria of mammalian cell synchrony. In: Fry, R.J.M., Griem, M.L., Kirsten, W.H. (Eds.): Normal and malignant cell growth. Recent results in cancer research, Vol. 17, pp. 90–103, Berlin-Heidelberg-New York: Springer-Verlag 1969.

    Google Scholar 

  • Sinclair, W.K., Morton, R.A.: X-ray and ultraviolet sensitivity of synchronized Chinese hamster cells at various stages of the cell cycle. Biophys. J. 5, 1–25 (1965).

    PubMed  CAS  Google Scholar 

  • Skipper, H.E., Schabel, F.M., Wilcox, W.S.: Experimental evaluation of potential anticancer agents. XXI. Scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells. Cancer Chemother. Rep. 51, 125–165 (1967).

    PubMed  CAS  Google Scholar 

  • Steel, G. G.: The kinetics of cell proliferation in tumours. In: Time and dose relationships in radiation biology as applied to radiotherapy, Brookhaven National Laboratory Publication BNL 50503 (C-57), pp. 130–140. Upton, New York (1970).

    Google Scholar 

  • Steward, P.G., Hahn, G.M.: The application of age response functions to the optimization of treatment schedules. Cell Tissue Kinet. 4, 279–291 (1971).

    PubMed  CAS  Google Scholar 

  • Stubblefield, E.: Synchronization methods for mammalian cell cultures. In: Prescott, D.M. (Ed.): Methods in cell physiology, New York: Academic Press 1968, pp. 25–43.

    Google Scholar 

  • Terasima, T., Tolmach, L.J.: Variations in several responses of Hela cells to X-irradiation during the division cycle. Biophys. J. 3, 11–33 (1963).

    PubMed  CAS  Google Scholar 

  • Terasima, T., Umezawa, H.: Lethal effects of bleomycin on cultured mammalian cells. J. Antibiotics 23, 300–304 (1970).

    CAS  Google Scholar 

  • Tobey, R.A.: Arrest of Chinese hamster cells in G2 following treatment with the anti-tumor drug bleomycin. J. cell. Physiol. 79, 259–266 (1972).

    PubMed  CAS  Google Scholar 

  • Tobey, R.A., Petersen, D.F., Anderson, E.C, Puck, T.T.: Life cycle analysis of mammalian cells. III. The inhibition of division in Chinese hamster cells by puromycin and actinomycin. Biophys. J. 6, 567–581 (1966).

    PubMed  CAS  Google Scholar 

  • Todd, P., Coohdll, T.P., Hellwell, A.B., Mahoney, J.A.: Post-irradiation properties of cultured Chinese hamster cells exposed to ultraviolet light. Radiat. Res. 38, 321–339 (1969).

    PubMed  CAS  Google Scholar 

  • Tyrer, D.D., Kline, I., Venditti, J.M., Goldin, A.: Separate and sequential chemotherapy of mouse leukemia L1210 with 1-β-D-arabinofuranosylcytosine hydrochloride and 1, 3-bis- (2-chloroethyl)-l-nitrosourea. Cancer Res. 27, 873–879 (1967).

    PubMed  CAS  Google Scholar 

  • Wagner, E.K., Roizman, B.: Effect of the Vinca alkaloids on RNA synthesis in human cells in vitro. Science 162, 569–570 (1968).

    PubMed  CAS  Google Scholar 

  • Walker, I.G., Helleiner, C.W.: The sensitivity of cultured mammalian cells in different stages of the division cycle to nitrogen and sulfur mustard. Cancer Res. 23, 734–739 (1963).

    PubMed  CAS  Google Scholar 

  • Wells, W., Winzler, R.J.: Metabolism of human leukocytes in vitro III. Incorporation of formate-14C into cellular components of leukemic human leukocytes. Cancer Res. 19, 1086–1090 (1959).

    PubMed  CAS  Google Scholar 

  • Westra, A., Dewey, W.C.: Variation in sensitivity to heat shock or X-rays during the cell cycle of Chinese hamster cells in vitro. Abstract to the Joint Meeting of the British Association for Radiation Research and the Netherlands Radiobiological Society, Oxford (1971).

    Google Scholar 

  • Whitmore, G.F., Borsa, J., Bacchetti, S., Graham, F.: Mammalian cell killing by inhibitors of DNA synthesis. In: Fry, R.J.M., Griem, M.L., Kirsten, W.H. (Eds.): Normal and Malignant Cell Growth. Recent results in cancer research, Vol. 17. pp. 109–117. New York: Springer-Verlag 1969.

    Google Scholar 

  • Young, R.S.K., Fisher, G.A.: The action of arabinosylcytosine on synchronously growing populations of mammalian cells. Biochem. biophys. Res. Comm. 32, 23–29 (1968).

    PubMed  CAS  Google Scholar 

  • Xeros, N.: Deoxyriboside control and synchronization of mitosis. Nature (Lond.) 194, 682–683 (1962).

    CAS  Google Scholar 

Download references

Authors
  1. H. Madoc-Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Mauro
    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

Madoc-Jones, H., Mauro, F. (1974). Site of Action of Cytotoxic Agents in the Cell Life Cycle. 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_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-65678-1_10

  • 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