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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1996 Jun;87(6):662–668. doi: 10.1111/j.1349-7006.1996.tb00274.x

Changes in Cell Proliferative Parameters of SCCVII and EMT6 Murine Tumors after Single‐dose Irradiation

Rumi Murata 1,✉, Yasumasa Nishimura 1, Yuta Shibamoto 2, Masahiro Hiraoka 1, Mitsuyuki Abe 3
PMCID: PMC5921140  PMID: 8766532

Abstract

To understand better the repopulation kinetics of tumor cells after radiotherapy, we Investigated changes in cell proliferative parameters after single‐dose irradiation of SCCVII tumors in C3H/He mice and EMT6 tumors in Balb/c mice. The following parameters were determined 0–15 days after single irradiation at 20 or 30 Gy; dividing fraction (DP), potential doubling time (Tpot), number of clonogenic cells per tumor (Ncln), and volume doubling time (Tvol). DF and Tpot were determined by in vivo‐in vitro cytokinesis‐block assay with cytochalasin B, Ncln was measured by in vivo‐in vitro colony‐forming assay, and Tvol was determined by growth delay assay. In both tumors, longer Tpot and lower DF and Ncln were obtained for 3–4 days after irradiation, but in SCCVII tumors these values returned to the pretreatment levels 9 days after irradiation. In EMT6 tumors, Tpot, DF, and Ncln did not return to the pretreatment levels even 12 days after irradiation. In the regrowth phase of both tumors following irradiation at 20 Gy, Tvol was longer than the pretreatment level, although Tpot was similar in SCCVII and only slightly longer in EMT6. Therefore, the cell loss factor in the regrowth phase was considered to be higher than the pretreatment level in both tumors. From the results, recruitment of previously quiescent cells into the proliferative pool in these tumors was suggested to contribute to repopulation after radiation.

Keywords: Cell kinetics, Repopulation, Radiation, Murine tumor, Potential doubling time

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REFERENCES

  • 1. ) Begg , A. C.Prediction of repopulation rates and radiosensitivity in human tumors . Int. J. Radiat. Biol. , 65 , 103 – 108 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) McNally , N. J.Can cell kinetic parameters predict the response of tumours to radiotherapy ? Int. J. Radiat. Biol. , 56 , 777 – 786 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Fowler , J. F.Potential for increasing the differential response between tumors and normal tissues: can proliferation rate be used ? Int. J. Radiat. Oncol. Biol Phys. , 12 , 641 – 645 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Trott , K. R. and Kummermehr , J.What is known about tumor proliferation rates to choose between accelerated fractionation or hyperfractionation ? Radiother. Oncol. , 3 , 1 – 9 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Trott , K. R.Cell repopulation and overall treatment time . Int. J. Radiat. Oncol. Biol. Phys. , 19 , 1071 – 1075 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Begg , A. C. , Hofland , I. , Moonen , L. , Bartelink , H. , Schraub , S. , Bontemps , P. , Le Fur , R. , van Den Bogaert , W. , Caspers , R. , van Glabbeke , M. and Horiot , J.The predictive value of cell kinetic measurements in a European trial of accelerated fractionation in advanced head and neck tumors: an interim report . Int. J. Radiat. Oncol. Biol Phys. , 19 , 1449 – 1453 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Begg , A. C. , Hofland , I. , van Glabbeke , M. , Bartelink , H. and Horiot , J.Predictive value of potential doubling time for radiotherapy of head and neck tumor patients: results from the EORTC Cooperative Trial 22851 . Semin. Radiat. Oncol. , 2 , 22 – 25 ( 1992. ). [Google Scholar]
  • 8. ) Speke , A. K. and Hill , R. P.Repopulation kinetics during fractionated irradiation and the relationship to the potential doubling time, Tpot . Int. J. Radiat. Oncol. Biol. Phys. , 31 , 847 – 856 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Begg , A. C. , Hofland , I. and Kummermehr , J.Tumour cell repopulation during fractionated radiotherapy: correlation between flow cytometric and radiobiological data in three murine tumours . Eur. J. Cancer , 27 , 537 – 543 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Allam , A. , Perez , L. A. , Huang , P. , Taghian , A. , Azinovic , I. , Freeman , J. , Duffy , M. , Efird , J. and Suit , H. D.The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice . Int. J. Radiat. Oncol. Biol. Phys. , 32 , 105 – 111 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Suit , H. D. , Howes , A. E. and Hunter , N.Dependence of response of a C3H mammary carcinoma to fractionated irradiation on fractionation number and intertreatment interval . Radiat. Res. , 72 , 440 – 454 ( 1977. ). [PubMed] [Google Scholar]
  • 12. ) Milas , L. , Yamada , S. , Hunter , N. , Guttenberger , R. and Thames , H. D.Changes in TCD50 as a measure of clonogen doubling time in irradiated and unirradiated tumors . Int. J. Radiat. Oncol. Biol. Phys. , 21 , 1195 – 1202 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Tsunemoto , H. , Ando , K. , Koike , S. and Urano , M.Repopulation of tumor cells following irradiation with X‐rays or low energy neutrons . Int. J. Radiat. Biol. , 65 , 255 – 261 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Rowley , R. , Hopkins , H. A. , Betsill , W. L. , Ritenour , E. R. and Looney , W. B.Response and recovery kinetics of a solid tumour after irradiation . Br. J. Cancer , 42 , 586 – 595 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Hill , R. P.Radiation‐induced changes in the in vivo growth rate of KHT sarcoma cells: implications for the comparison of growth delay and cell survival . Radiat. Res. , 83 , 99 – 108 ( 1980. ). [PubMed] [Google Scholar]
  • 16. ) Rofstad , E. K.Repopulation between radiation fractions in human melanoma xenografts . Int. J. Radiat. Oncol. Biol. Phys. , 23 , 63 – 68 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Javed‐Afzal , S. M. , Tenforde , T. S. , Kavanau , K. S. and Curtis , S. B.Repopulation kinetics of rat rhabdomyosarcoma tumors following single and fractionated doses of low‐LET and high‐LET radiation . Radiat. Res. , 127 , 230 – 233 ( 1991. ). [PubMed] [Google Scholar]
  • 18. ) Hermens , A. F. and Barendsen , G. W.Changes of cell proliferation characteristics in a rat rhabdomyosarcoma before and after X‐irradiation . Eur. J. Cancer , 5 , 173 – 189 ( 1969. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Ang , K. K. , Thames , H. D. , Jones , S. D. , Jiang , G. L. , Milas , L. and Peters , L. J.Proliferation kinetics of a murine fibrosarcoma during fractionated irradiation . Radiat. Res. , 116 , 327 – 336 ( 1988. ). [PubMed] [Google Scholar]
  • 20. ) Jung , H. , Kruger , H. J. , Brammer , I. , Zywietz , F. and Beck‐Bornholdt , H. P.Cell population kinetics of the rhabdomyosarcoma R1H of the rat after single doses of X‐rays . Int. J. Radiat. Biol. , 57 , 567 – 589 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Szczepanski , L. and Trott , K. R.Post‐irradiation proliferation kinetics of a serially transplanted murine adenocarcinoma . Br. J. Radiol. , 48 , 200 – 208 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Fenech , M. and Morley , A. A.Measurement of micronuclei in lymphocytes . Mutat. Res. , 147 , 29 – 36 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Shibamoto , Y. and Streffer , C.Estimation of the dividing fraction and potential doubling time of tumors using cytochalasin B . Cancer Res. , 51 , 5134 – 5138 ( 1991. ). [PubMed] [Google Scholar]
  • 24. ) Shibamoto , Y. , Shibata , T. , Miyatake , S. , Oda , Y. , Manabe , T. , Ohshio , G. , Yagi , K. , Streffer , C. , Takahashi , M. and Abe , M.Assessment of the proliferative activity and radiosensitivity of human tumors using the cytokinesis‐block micronucleus assay . Br. J. Cancer , 70 , 67 – 71 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Hirst , D. G. , Brown , J. M. and Hazlehurst , J. L.Enhancement of CCNU cytotoxicity by misonidazole: possible therapeutic gain . Br. J. Cancer , 46 , 109 – 116 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. ) Rockwell , S. C. , Kallman , R. F. and Fajardo , L. F.Characteristics of a serially transplanted mouse mammary tumor and its tissue‐culture‐adapted derivative . JNCI , 49 , 735 – 749 ( 1972. ). [PubMed] [Google Scholar]
  • 27. ) Nishimura , Y. and Urano , M.Timing and sequence of hyperthermia in fractionated radiotherapy of a murine fibrosarcoma . Int. J. Radiat. Oncol Biol. Phys. , 27 , 605 – 611 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Steel , G. G.Cell loss from experimental tumors . Cell Tissue Kinet. , 1 , 193 – 207 ( 1968. ). [Google Scholar]
  • 29. ) Masunaga , S. , Ono , K. and Abe , M.A method for selective measurement of the radiosensitivity of quiescent cells in solid tumors, combination of immunofluorescence staining to BrdU and micronucleus assay . Radiat. Res. , 125 , 243 – 247 ( 1991. ). [PubMed] [Google Scholar]
  • 30. ) Fowler , J. F.Rapid repopulation in radiotherapy: a debate on mechanism. The phantom of tumor treatment, continually rapid proliferation unmasked . Radiother. Oncol. , 22 , 156 – 158 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Trott , K. R. and Kummermehr , J.Split dose recovery of a mouse tumour and its stroma during fractionated irradiation . Br. J. Radiol. , 55 , 841 – 846 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 32. ) Vermund , H.The significance of the tumour bed reaction in the radiation treatment of malignant tumours . Radiology , 82 , 678 – 687 ( 1959. ). [PubMed] [Google Scholar]

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