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Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells

  • Preclinical Studies
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Abstract

The cytotoxic activity of various chemotherapy agents was investigated in asynchronous populations of cultured 9L rat brain tumor cells, and as a function of their position in the cell cycle. Representative drugs from the classes of DNA-active agents, alkylating agents, spindle poisons, and antimetabolites were tested. The ability to induce cell lethality in asynchronous populations as a function of drug concentration varied for 1 hr pulse exposures. In order of decreasing cytotoxic activity, DHAQ was the most effective, followed by VCR, VDS, VBL, ADR, BCNU, cis-DDP, BLM, DBD, RZ, and HU. The effect of chemotherapy agents on synchronous 9L cells obtained by mitotic selection also varied with respect to the individual agent and was cell cycle-dependent. Survival age-responses ranged from being minimal to demonstrating significant fluctuations as a function of cell cycle position. For all agents except ADR and HU, the sensitivity of G1 phase was greater than S phase. RZ exhibited essentially a flat age-response. Comparison of the cell cycle age-responses of chemotherapeutic agents to those exhibited by the cytotoxic modalities of radiation and hyperthermia demonstrate several unique differences.

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Abbreviations

ADR:

Adriamycin

BCNU:

1,3-Bis (2-Chloroethyl)-1-Nitrosourea

BLM:

Bleomycin sulfate

cis-DDP:

cis-Dichlorodiamineplatinum

DHAQ:

Dihydroxy anthraquinone

DBD:

Dibromodulcitol

HU:

Hydroxyurea

RZ:

Razoxane

VBL:

Vinblastine Sulfate

VCR:

Vincristine Sulfate

VDS:

Vindesine Sulfate

HBSS:

Hanks' Balanced Salt Solution

References

  1. Drewinko B, Barlogie B: The relevance of cell kinetics in determining drug activity in vitro. In: C Nicolini (ed) Cell Growth. Plenum Press: New York, pp 749–772, 1982

    Google Scholar 

  2. Valeriote FA: The use of cell kinetics in the development of drug combinations. Pharm Ther 4:1–33, 1979

    Google Scholar 

  3. Wheeler KT, Tel N, Williams ME, Sheppard S, Levin VA, Kabra PM: Factors influencing the survival of rat brain tumor cells following in vitro treatment with 1,3-bis (2chloroethyl)-1-nitrosourea. Cancer Res 35:1464–1469, 1975

    Google Scholar 

  4. Nomura K, Hoshino T, Knebel K, Deen DF, Barker M: BCNU-induced perturbations in the cell cycle of 9L rat brain tumor cells. Cancer Treat Rep 62:747–754, 1978

    Google Scholar 

  5. Hoshino T, Wilson CB: Cell kinetic analysis of human malignant brain tumors (gliomas). Cancer 44:6956–6962, 1979

    Google Scholar 

  6. Marton LJ, Levin VA, Hervatin SJ, Kock-Wesser J, McCann PP, Sjoerdsma A: Potentiation of the antitumor therapeutic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea by α-difluoromethylornithine, an ornithine decarboxylase inhibitor. Cancer Res 41:4426–4431, 1981

    Google Scholar 

  7. Hoshino T, Deen DF, Williams MR, Sano Y: Differential response of elutriated 9L cells to treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea. Cancer Res 41:4404–4407, 1981

    Google Scholar 

  8. Bjerkvig R, Oredsson SM, Marton LJ, Linden M, Deen DF: Cel cycle age responses of 9L cells to 1,3-bis(2-chloro ethyl)-1-nitrosourea and modification by α-difluoromethyl ornithine. Cancer Res 43:1497–1500, 1983

    Google Scholar 

  9. Nomura K, Hoshino T, Deen DF, Knebel KD: Perturbed cell kinetics of 9L rat brain tumor cells following dianhydrogalactitol. Cancer Treat Rep 62:2055–2061, 1978

    Google Scholar 

  10. Deen DF, Hoshino T, Williams ME, Nomura K, Bartle PM: Response of 9L tumor cells in vitro to spirohydantoin mustard. Cancer Res 39:4336–4340, 1979

    Google Scholar 

  11. Oredsson SM, Deen DF, Marton LJ: Decreased cytotoxicity of cis-diammine-dichloroplatinum (II) by α-difluoro-methylornithine depletion of polyamines in 9L rat brain tumor cells in vitro. Cancer Res 42:1296–1299, 1982

    Google Scholar 

  12. Keng PC, Wheeler KT:Radiation response of synchronized 9L rat brain tumor cells separated by centrifugal elutriation. Radiat Res 83:633–643, 1980

    Google Scholar 

  13. Kimler BF, Henderson SD: Cyclic responses of cultured 9L cells to radiation. Radiat Res 91:155–168, 1982

    Google Scholar 

  14. Zar JH: Biostatistical Analysis, pp. 198–235. Englewood Cliffs, NJ: Prentice-Hall, Inc 1974

    Google Scholar 

  15. Kimler BF, Cheng CC: Comparison of the effects of dihydroxyanthraquinone and Adriamycin on the survival of cultured Chinese hamster cells. Cancer Res 42:3631–3636, 1982

    Google Scholar 

  16. Umezawa H, Ishizuka M, Maeda K, Takeuchi T: Studies on bleomycin. Cancer 20:891–895, 1967

    Google Scholar 

  17. Burger RM, Peisach J, Horwitz SB: Mechanisms of bleomycin action: in vitro studies. Life Science 28:715–727, 1981

    Google Scholar 

  18. Henderson SD, Kimler BF, Scanlon MF: Interaction of hyperthermia and radiation on the survival of synchronous 9L cells. Radiat Res 92:146–159, 1982

    Google Scholar 

  19. Henderson SD, Kimler BF: Response of cultured 9L cells to bleomycin and X-rays. (Abstract) Radiat Res 83:371, 1980

    Google Scholar 

  20. Twentyman PR: Bleomycin — mode of action with particular reference to the cell cycle. Pharmac Ther 23:417–441, 1984

    Google Scholar 

  21. Gridna DJ, Sigdestad CP, Peters LJ: Cytotoxic effect in vivo of selected chemotherapeutic agents on synchronized murine fibrosarcoma cells. Br J Cancer 42:677–683, 1980

    Google Scholar 

  22. Barranco SC: Cellular and molecular effects of adriamycin on dividing and nondividing cells. Pharmac Ther 24:303–319, 1984

    Google Scholar 

  23. Meyn R, Murray D: Cell cycle effects of alkylating agents. Pharmac Ther 24:147–163, 1984

    Google Scholar 

  24. Drewinko B, Gottlieb JA: Action of cis-dichlorodiammine-platinum (II) (NSC 119875) at the cellular level. Cancer Chemother Rep 59:655–673, 1975

    Google Scholar 

  25. Kimler BF: Interaction of razoxane and radiation on cultured Chinese hamster cells. Int J Radiat Oncol Biol Phys 8:1333–1338, 1982

    Google Scholar 

  26. Traganos F, Evenson DP, Staino-Coico L, Darzynkiewicz F, Melamed MR: Action of dihydroxyanthraquinone on cell cycle progression and survival of a variety of cultured mammalian cells. Cancer Res 40:671–681, 1980

    Google Scholar 

  27. 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

    Google Scholar 

  28. Olah E, Polyi I, Sugar J: Effects of cytostatics on proliferating and stationary cultures of mammalian cells. Eur J Cancer 14:895–900, 1978

    Google Scholar 

  29. Wibe E: Age-dependent cell inactivation by vincristine alone or in combination with 1-propargyl-5-chloropyrimidin-2-one. Cancer Res 40:2069–2073, 1980

    Google Scholar 

  30. Sinclair WK: Hydroxyurea: Differential lethal effects on cultured mammalian cells during the cell cycle. Science 150:1729–1731, 1965

    Google Scholar 

  31. Kim JH, Gelbind AS, Perez AG: Action of hydroxyurea on the nucleic acid metabolism and viability of HeLa cells. Cancer Res 27:1301–1305, 1967

    Google Scholar 

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Authors and Affiliations

  1. Radiation Biology Laboratory, Department of Radiation Oncology, University of Kansas Medical Center, 66103, Kansas City, KS, USA

    Sheri D. Henderson, Brace F. Kimler & Mary L. Barnes

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  1. Sheri D. Henderson
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  2. Brace F. Kimler
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  3. Mary L. Barnes
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Henderson, S.D., Kimler, B.F. & Barnes, M.L. Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells. Invest New Drugs 5, 145–154 (1987). https://doi.org/10.1007/BF00203539

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