Skip to main content
Log in

The effects of 1-methyl-1-nitrosourea on the survival pattern of cycling and noncycling HeLa cells

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

The biological behavior of HeLa cells exposed to 1-methyl-1-nitrosourea was examined by determining the survival fraction in asynchronous and synchronous cultures. Asynchronous cell population exposed to 1-methyl-1-nitrosourea for 1 h exhibited a shoulder type survival curve, indicating that damage must be accumulated before the lethal effect occurs. A fraction of 25% of cells survives the concentration of 100 μg/ml. The duration of treatment with the drug did not have a significant effect on the cell survival. The experiments with synchronized cells showed that MNU exhibits the killing in all phases of the cell age, but the most sensitive are these in S phase. However, they are still six times more resistant at the same concentration than the culture in plateau phase. At the concentration of 100 μg/ml nondividing plateau cells are about 35 times more sensitive than exponentially growing cells. We can conclude that MNU acts as the most active killing agents on the cells which are in nondividing plateau phase.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ban, J., Han, A., Korbelik, M.: An improves method for cell cycle analysis of synchronized mammalian cells (HeLa-FA 3). Iug. Phys. Pharm. Acta 10, 173–181 (1974)

    Google Scholar 

  • Ban, J., Brdar, B.: 1-Methyl-1-nitrosourea: I. Effects on the synthesis of nucleic acids and protein in cultured cells and some RNA-viruses. Period. Biol. 80, 41–47 (1978)

    Google Scholar 

  • Barranco, S.C., Humphrey, R.M.: The effects of 1,3-Bis(2-chloroethyl)-1-nitrosourea on survival and cell progression in Chinese hamster cells. Cancer Res. 31, 191–195 (1971a)

    Google Scholar 

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

    Google Scholar 

  • Barranco, S.C., Novak, J.K., Humphrey, R.M.: Response of mammalian cells following treatment with bleomycin and 1,3-Bis(2-chloroethyl)-1-nitrosourea during plateau phase. Cancer Res. 33, 691–694 (1973)

    Google Scholar 

  • Barranco, S.C., Novak, J.K., Humphrey, R.M.: Studies on recovery from chemically induced damage in mammalian cells. Cancer Res. 35, 1194–1204 (1975)

    Google Scholar 

  • Barranco, S.C., Haenelt, B.R., Bolton, W.E.: Cell cycle time determinations based on liquid scintillation counting of 3H-TdR labeled mitotic cells. Cell Tissue Kinet. 10, 335–340 (1977)

    Google Scholar 

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

    Google Scholar 

  • Bhuyan, B.K., Fraser, T.J., Day, K.J.: Cell proliferation kinetics and drug sensitivity of exponential and stationary populations of cultured L 1210 cells. Cancer Res. 37, 1057–1063 (1977)

    Google Scholar 

  • Brdar, B., Ban, J.: Inhibition of viral RNA synthesis by 1-methyl-1-nitrosourea. Eur. J. Canc. (sub. for publ.)

  • Carter, S.K., Schabel, F.M., Broder, L.E., Johnston, T.P.: 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) and other nitrosoureas in cancer treatment: A review. In: G. Klein and S. Weinhouse (eds.), Advances in cancer research, Vol. 16, pp. 273–332. New York: Academic Press 1972)

    Google Scholar 

  • Cox, R., Irving, C.C.: Effect of N-methyl-N-nitrosourea on the DNA of rat bladder epithelium. Cancer Res. 36, 4114–4118 (1976)

    Google Scholar 

  • Drewinko, B., Loo, T.L., Gottlieb, J.A.: A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells. Cancer Res. 36, 511–515 (1976)

    Google Scholar 

  • Elkind, M.M., Whitemore, G.F.: The radiobiology of cultured mammalian cells. New York: Gordon and Beach 1967

    Google Scholar 

  • Emanuel, N.M., Vermel, E.M., Ostrovskaya, L.A., Korman, N.P.: Experimental and clinical studies of the antitumor activity of 1-methyl-1-nitrosourea (NSC-23909). Cancer Chem. Rep. 58, 135–148 (1974)

    Google Scholar 

  • Frei, J.V.: Toxicity tissue changes, and tumor induction in inbred Swiss mice by methylnitrosoamine and-anide compounds. Cancer Res. 30, 11–17 (1970)

    Google Scholar 

  • Hahn, G.M., Gordon, L.F., Kurkjian, S.D.: Response of cycling and noncycling cells to 1,3-Bis(2-chloroethyl)-1-nitrosourea and to bleomycin. Cancer Res. 34, 2373–2377 (1974)

    Google Scholar 

  • Han, A., Korbelik, M., Ban, J.: DNA-to-protein cross-linking in synchronized HeLa cells exposed to ultra-violet light. Int. J. Radiat. Biol. 27, 63–74 (1975)

    Google Scholar 

  • Han, A., Sinclair, W.K., Kimler, B.F.: The effect of N-ethylmaleimide on the response to X-rays of synchronized HeLa cells. Radiat. Res. 65, 337–350 (1976)

    Google Scholar 

  • Howard, A., Pelc, S.R.: Synthesis of DNA in normal and irradiated cells and its relation to chromosome breakage. Heredity 6, 261–265 (1953)

    Google Scholar 

  • Kann, H.E., Kohn, K.W., Lyles, J.M.: Inhibition of DNA repair by the 1,3-bis(2-chloroethyl)-1-nitrosourea breakdown product, 2-chloroethyl isocyanate. Cancer Res. 34, 398–402 (1974)

    Google Scholar 

  • Kirtikar, D.M., Goldthwait, D.A.: The enzymatic release of 6D-methylguanine and 3-methyladenine from DNA reacted with the carcinogen N-methyl-N-nitrosourea. Proc. Natl. Acad. Sci. U.S. 71, 2022–2026 (1974)

    Google Scholar 

  • Kleihues, P.: Blockierung der DNS-Synthese durch N-methyl-N-nitroso-Harnstoff in vivo. Arzneim. Forsch. 19, 1041–1043 (1969)

    Google Scholar 

  • Kleilhues, P., Margison, G.P.: Exhaustion and recovery of repair excision of O6-methylguanine from rat liver DNA. Nature 259, 153–155 (1976)

    Google Scholar 

  • Kolarić, K.: Combination chemotherapy with 1-methyl-1-nitrosourea (MNU) and cyclophosphamide in solid tumors. Z. Krebsforsch. 89, 311–319 (1977)

    Google Scholar 

  • Lawley, P.D., Shah, S.A.: Methylation of DNA by 3H-14C-methyl-labelled N-methyl-N-nitrosourea. Evidence for transfer of the intact methyl group. Chem. Biol. Interactions 7, 115–120 (1973)

    Google Scholar 

  • Plant, J.E., Roberts, J.J.: Novel mechanism for the inhibition of DNA synthesis following methylation. Effect of N-methyl-N-nitrosourea on HeLa cells. Chem. Biol. Interactions 3, 337–324 (1971)

    Google Scholar 

  • Plant, J.E., Roberts, J.J.: Extension of the pre-DNA synthetic phase of the cell cycle as a consequence of DNA alkylation in Chinese hamster cells. Possible mechanism of DNA repair. Chem. Biol. Interactions 3, 343–351 (1971)

    Google Scholar 

  • Roberts, J.J., Pascoe, J.M., Plant, J.E., Sturrock, J.E., Crathorn, A.R.: Quantitative aspects of the repair of alkylated DNA in cultured mammaian cells, I. Effect on HeLa and Chinese hamster cell survival of alkylation of cellular macromolecules. Chem. Biol. Interactions 3, 29–47 (1971)

    Google Scholar 

  • Schabel, F.M. Jr., Johnston, T.P., McCabel, G.S.: Experimental evaluation of potential anticancer agents. VIII. Effects of certain nitrosoureas on intracerebral L 1210 leukemia. Cancer Res. 23, 725–733 (1963)

    Google Scholar 

  • Serebryanyi, A.M., Smotraeva, M.A., Kruglyakova, K.A., Kostyanovskii, R.G.: Carbamoylation of DNA in N-nitroso-N-methylurea. Dokl. Akad. Nauk SSSR 185, 817–819 (1969)

    Google Scholar 

  • Skinner, W.A., Gram, H.F., Green, M.O.: Potential anticancer agents. XXXI. The relationship of chemical structure to antileukemic activity with analogs of 1-methyl-3-nitro-1-nitrosoguanidine (NCS-9369). J. Med. Chem. 2, 299–333 (1960)

    Google Scholar 

  • Terasima, T., Tolmach, L.: Growth and nucleic acids synthesis in synchronously dividing populations of HeLa cells. Exp. Cell Res. 30, 344–362 (1963)

    Google Scholar 

  • Tobey, R.A., Crissman, H.A.: Comparative effects of three nitrosourea derivatives on mammalian cell cycle progression. Cancer Res. 35, 460–470 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ban, J., Brdar, B. & Sorić, J. The effects of 1-methyl-1-nitrosourea on the survival pattern of cycling and noncycling HeLa cells. J Cancer Res Clin Oncol 94, 265–275 (1979). https://doi.org/10.1007/BF00419286

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00419286

Key words

Navigation