Mathematical Models of Carcinogenesis and Tumor Growth in an Experimental Rat Colon Adenocarcinoma

  • Alain P. Maskens
Part of the Sloan-Kettering Institute Cancer Series book series (SKICS)


An accurate assessment of the growth behavior of cancers is of invaluable help in the understanding of their biological and clinical properties, as well as in the planning of appropriate therapies. Yet, in the important field of colorectal tumors, little such quantitative information is available, because of the inaccessibility of those lesions for direct serial measurements.


Colon Carcinogenesis Tritiated Thymidine Macroscopic Tumor Chemical Carcinogenesis Exponential Growth Rate 
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  1. Armitage, P., and Doll R., 1954, The age distribution of cancer and a multi-stage theory of carcinogenesis, Br. J. Cancer 8: 1–12.PubMedCrossRefGoogle Scholar
  2. Armitage, P., and Doll R., 1957, A two-stage theory of carcinogenesis in relation to the age distribution of human cancer, Br. J. Cancer 11: 161–169.CrossRefGoogle Scholar
  3. Ashley, D. J. B., 1969, The two “hit” and multiple “hit” theories of carcinogenesis, Br. J. Cancer 23: 313.PubMedCrossRefGoogle Scholar
  4. Berenblum, I., 1974, Chemical carcinogenesis as a biological problem, in: Frontiers in Biology, Vol. 27, North-Holland, Amsterdam.Google Scholar
  5. Berenblum, I., and Shubik, P., 1949, An experimental study of the initiating stage of carcinogenesis, and a re-examination of the somatic cell mutation theory of cancer, Br. J. Cancer 3: 109–118.PubMedCrossRefGoogle Scholar
  6. Burch, P. R. J., 1962, A biological principle and its converse some implications for Carcinogenesis, Nature (London) 195: 241–243.CrossRefGoogle Scholar
  7. Burdette, W., 1974, Colorectal carcinogenesis, Cancer 34: 872–877.PubMedCrossRefGoogle Scholar
  8. Chomcai, C., Bhadrachari, N., and Nigro, N. D., 1974, The effect of bile on the induction of experimental intestinal tumors in rats, Colon Rectum 17: 310–312.CrossRefGoogle Scholar
  9. Clifton, K. H., and Yatvin, M. B., 1970, Cell population growth and cell loss in the MTG-B mouse mammary carcinoma, Cancer Res. 30: 658–664.PubMedGoogle Scholar
  10. Cohen, D., and Steel, G. G., 1972, Thymidine labelling studies in a transmissible veneral tumour of the dog, Br. J. Cancer 26: 413–419.Google Scholar
  11. Dethlefsen, L., Prewitt, J., and Mendelsohn, M., 1968, Analysis of tumor growth curves, J. Natl. Cancer Inst. 40: 389–405.Google Scholar
  12. Druckrey, H., 1970, Production of colonic carcinomas by 1, 2 dimethylhydrazines and azoxyalkanes, in: Carcinoma of the Colon and Antecedent Epithelium ( W. J. Burdette, ed.), pp. 267–279, Thomas, Springfield, Ill.Google Scholar
  13. Druckrey, H., 1971, Genotypes and phenotypes of ten inbred strains of BD-rats, Arzneim. -Forsch. (Drug Res.) 21: 1274–1278.Google Scholar
  14. Druckrey, H., 1973, Specific carcinogenic and teratogenic effects of “indirect” alkylating methyl and ethyl compounds, and their dependency on stages of ontogenic developments, Xenobiotica 3: 271–303.CrossRefGoogle Scholar
  15. Druckrey, H., and Lange, A., 1972, Carcinogenicity of azoxymethane dependent on age in BD rats, Fed. Proc. 31: 1482–1484.PubMedGoogle Scholar
  16. Druckrey, H., Preussman, R., Matzkies, F., and Ivankovic, S., 1967, Selektive Erzeugung von Darmkrebs bei Ratten durch 1, 2-Dimethylhydrazin, Naturwissenchaften 58: 285–286.Google Scholar
  17. Fiala, E. G., 1975, Investigation into the metabolism and mode of action of the colon carcinogen 1,2-dimethylhydrazin, Cancer 36: 2407–2412.PubMedCrossRefGoogle Scholar
  18. Fisher, J. C., 1958, Multiple-mutation theory of carcinogenesis, Nature (London) 181: 651–652.CrossRefGoogle Scholar
  19. Frindel, E., Malaise, E., Alpen, E., and Tubiana, M., 1967, Kinetics of cell proliferation of an experimental tumor, Cancer Res. 27: 1122–1131.PubMedGoogle Scholar
  20. Gennaro, A. R., Villanueva, R., Sukonthaman, Y., Vathanophas, and Rosemond, G. P., 1973, Chemical carcinogenesis in transposed intestinal segments, Cancer Res. 33: 536–541.PubMedGoogle Scholar
  21. Griswold, D. P., Jr., Simpson-Herren, L., and Schabel, F. M., Jr., 1970, Altered sensitivity of a ramster plasmacytoma to cytosine arabinoside (NSC-63878), Cancer Chemother. Rep. 54: 337–340.Google Scholar
  22. Haase, P., Cowen, D. M., Sr., Knowles, J. C., and Cooper, E. H., 1973, Evaluation of dimethylhydrazine induced tumors in mice as a model system for colorectal cancer, Br. J. Cancer 28: 530–543.PubMedCrossRefGoogle Scholar
  23. Hawks, A., and Magee, P., 1974, The alkylation of nucleic acids of rat and mouse in vivo by the carcinogen 1,2-dimethylhydrazine, Br. J. Cancer 30: 440–447.PubMedCrossRefGoogle Scholar
  24. Hawks, A., Hicks, R., Holsman, J., and Magee, P., 1974, Morphological and biochemical effects of 1,2-dimethylhydrazine and 1-methylhydrazine in rats and mice, Br. J. Cancer 30: 429–439.PubMedCrossRefGoogle Scholar
  25. Heidelberg, C., 1973, Current trends in chemical carcinogenesis, Fed. Proc. 32: 2154–2161.Google Scholar
  26. Hermens, A. F., and Barendsen G. W., 1969, Changes of cell proliferation characteristics in a rat rhabdomyosarcoma before and after X-irradiation, Eur. J. Cancer 5: 173–189.PubMedGoogle Scholar
  27. Huemer, R. P., and Bickert, C., 1971, Growth and differentiation of a transplantable plasmacytoma, Oncology 25: 439–445.PubMedCrossRefGoogle Scholar
  28. Kanagalingam, K., and Balis, A. E., 1975, In vivo repair of rat intestinal DNA damage by alkylating agents, Cancer 36: 2364–2372.PubMedCrossRefGoogle Scholar
  29. Killmann, S. A., Cronkite, E. P., Fliedner, T. M., and Bond, V. P., 1962, Cell proliferation in multiple myeloma studied with tritiated thymidine in vivo, Lab. Invest. 11: 845–851.PubMedGoogle Scholar
  30. Knudson, A. G., 1971, Mutation and cancer: Statistical study of retinoblastoma, Proc. Natl. Acad. Sci. USA 68: 820–823.PubMedCrossRefGoogle Scholar
  31. Knudson, A. G., 1973, Mutation and human cancer, in: Advances in Cancer Research, Vol. 17 ( G. Klein and S. Weinhouse, eds.), pp. 317–352, Academic Press, New York.CrossRefGoogle Scholar
  32. Laird, A., 1964, Dynamics of tumor growth, Br. J. Cancer 18: 490–502.Google Scholar
  33. Laird, A., 1969, Dynamics of growth in tumors and in normal organisms, Natl. Cancer Inst. Monogr. 30: 15–28.Google Scholar
  34. Magee, P. N., 1974, Molecular Mechanisms in chemical carcinogenesis, in: Special Topics in Carcinogenesis (E. Grundmann, ed.), pp. 2–8, Vol. 44 of Recent Results in Cancer Research, Springer-Verlag, New York.Google Scholar
  35. Martin, M. S., Martin, F., Michiels, R., Bastien, H., Justrabo, E., Bordes, M., and Viry, B., 1973, An experimental model for cancer of the colon and rectum, Digestion 8: 22–34.PubMedCrossRefGoogle Scholar
  36. Martin, M. S., Martin, F., Justrabo, E., Knopf, J.-F., Bastien, H., and Knobel, S., 1974, Induction de cancers coliques chez le rat par injection unique de 1,2-dimethylhydrazine, Biol. Gastroenterol. 7: 37–42.Google Scholar
  37. Maskens, A., 1976, Histogenesis and growth pattern of 1,2-dimethylhydrazine induced rat colon adenocarcinoma, Cancer Res. 36: 1585–1592.PubMedGoogle Scholar
  38. Maskens, A., Meersseman, F., and Rahier, J., 1975, Growth rate of 1,2-dimethylhydrazine induced colon adenocarcinoma in rat (abstr.), Proc. Am. Assoc. Cancer Res. 16: 17.Google Scholar
  39. Matsumoto, H., and Higa, H., 1966, Studies on methylazoxymethanol, the aglycone of cycasin: Methylation of nucleic acids in vitro, Biochem. J. 98: 20c - 22c.PubMedGoogle Scholar
  40. McCredie, J., Inch, W., Kruuv, J., and Watson, T., 1965, Growth 29: 331–347.Google Scholar
  41. McCredie, J. A., Inch, W. R., and Sutherland, R. M., 1971, Differences in growth and morphology between the spontaneous C3H mammary carcinoma in the mouse and its syngeneic transplants, Cancer 27: 635–642.PubMedCrossRefGoogle Scholar
  42. Mendelsohn, M., 1960, The growth fraction: A new concept applied to tumors, Science 132: 1496.Google Scholar
  43. Mendelsohn, M., 1962, Autoradiographic analysis of cell proliferation in spontaneous breast cancer of C3H mouse. III. The growth fraction, J. Natl. Cancer Inst. 28: 1015–1029.Google Scholar
  44. Mendelsohn, M., 1963, Cell proliferation and tumour growth, in: Cell Proliferation ( L. F. Lamerton and R. J. M. Fry, eds.), pp. 190–210, Blackwell, London.Google Scholar
  45. Miller, J. A., 1970, Carcinogenesis by chemicals: An overview, G. H. A. Clowes Memorial Lecture, Cancer Res. 30: 559–576.Google Scholar
  46. Nigro, N. D., Bhadrachari, N., and Chomcai, C., 1973, A rat model for studying colonic cancer, Dis. Colon Rectum 16: 438–443.Google Scholar
  47. Nordling, C. O., 1953, A new theory on the cancer inducing mechanism, Br. J. Cancer 7: 68–72.Google Scholar
  48. Pozharisski, K., and Klimashevski, V., 1974, Comparative morphological and histoautoradiographic study of multiple experimental intestinal tumours, Exp. Pathol. 9: 88–98.Google Scholar
  49. Pozharisski, K., Kapustin, Y., Likhachev, A., and Shaposhnikov, J., 1975, The mechanism of carcinogenic action of 1,2-dimethylhydrazine ( SDMH) in rats, Int. J. Cancer 15: 673–683.Google Scholar
  50. Preussmann, R., 1974, Formation of carcinogens from precursors occurring in the environment; new aspects of nitrosamine induced tumorigenesis, in: Special Topics in Carcinogenesis (E. Grundmann, ed.), pp. 9–15, Vol. 44 of Recent Results in Cancer Research, Springer-Verlag, New York.Google Scholar
  51. Reddy, B., Weisburger, J., Narisawa, T., and Wynder, E., 1974a, Colon carcinogenesis in germ free rats with 1,2-dimethylhydrazine and N-methyl-N’-nitro-N-nitrosoguanidine, Cancer Res. 34: 2368–2372.PubMedGoogle Scholar
  52. Reddy, B., Weisburger, J., and Wynder, E., 1974b, Effects of dietary fat level and dimethylhydrazine on fecal acid and neutral sterol excretion and colon carcinogenesis in rats, J. Natl. Cancer Inst. 52: 507–511.Google Scholar
  53. Ryser, H. J. P., 1971, Chemical carcinogenesis, N. Eng. J. Med. 285: 721–734.Google Scholar
  54. Schauer, A., Vollnagel, T., and Wildanger, F. 1969, Cancerisierung des Rattendarmes durch 1, 2-Dimethylhydrazine, Ztschr. Ges. Exp. Med. 150: 87–93.Google Scholar
  55. Schauer, A., Kunze, E., and Boxler, K., 1971, Generationszeitzyklus 1,2- Dimethylhydrazin-induzierten Adenocarcinomen des Rattencolon, Naturwissenschaften 58: 221.PubMedCrossRefGoogle Scholar
  56. Shank, R. C., and Magee, P. N., 1967, Similarities between the biochemical actions of cycasin and dimethylnitrosamine, Biochem. J. 105: 521–527.Google Scholar
  57. Simpson-Herren, L., and Lloyd, H., 1970, Kinetic parameters and growth curves for experimental tumor systems, Cancer Chemother. Rep. 54: 143–174.Google Scholar
  58. Simpson-Herren, L., Sanford, A., and Holmquist, J., 1974, Cell population kinetics of transplanted and metastatic Lewis lung carcinoma, Cell Tissue Kinet. 7: 349–361.Google Scholar
  59. Smith, D., 1966, Mutagenicity of cycasin aglycone (methylazoxymethanol), a naturally occurring carcinogen, Science 152: 1273–1274.Google Scholar
  60. Springer, P., Springer, J., and Oehlert, W. 1970, Die Vorstufen des 1,2Dimethylhydrazin-induzierten Dick-und Dundarmcarcinoms der Ratte, Ztschr. Krebsforsch. 74: 236–240.Google Scholar
  61. Steel, G., 1967, Cell loss as a factor in the growth rate of human tumours, Eur. J. Cancer 3: 381387.Google Scholar
  62. Stocks, P., 1953, A study of the age curve for cancer of the stomach in connection with a theory of the cancer producing mechanism, Br. J. Cancer 7: 407–417.Google Scholar
  63. Sullivan, P. W., and Salmon, S. E., 1972, Kinetics of tumor growth and regression in Ig G multiple myeloma. J. Clin. Invest. 51: 1697–1708.Google Scholar
  64. Teas, J., and Dyson, J. G., 1967, Mutation in Drosophila by methylazoxymethanol, the aglycone of cycasin, Proc. Soc. Exp. Biol. Med. 125: 988–990.Google Scholar
  65. Thurnherr, N., Deschner, E., Stonehill, E., and Lipkin, M., 1973, Introduction of adenocarcinomas of the colon in mice by weekly injections of 1,2-dimethylhydrazine, Cancer Res. 33:940–945Google Scholar
  66. Ward, J. M., Yamamoto, R. S., and Brown, C. A., 1973a, Pathology of intestinal neoplasms and other lesions in rats exposed to azoxymethane, J. Natl. Cancer Inst. 51: 1029–1035.Google Scholar
  67. Ward, J. M., Yamamoto, R S., and Weisburger, J. H., 1973b, Cellulose dietary bulk andazoxymethane induced intestinal cancer,J Natl. Cancer Inst. 51: 713–715.Google Scholar
  68. Weisburger, J., 1971, Colon carcinogens: Their metabolism and mode of action, Cancer 28: 60–70.Google Scholar
  69. Welin, S., Youker, J., and Spratt, J., 1963, The rates and patterns of growth of 375 tumors of the large intestine and rectum observed serially by double contrast enema study ( Malmö tech-nique ), Am. J. Roentgen Radium Ther. Nucl. Med. 90: 673–687.Google Scholar
  70. Wiebecke, B., Löhrs, U., Gimmy, J., and Eder, M., 1969, Erzeugung von Darmtumoren beim Mausen durch 1,2-Dimethylhydrazin, Ztschr. Ges. Exp. Med. 149: 277–278.CrossRefGoogle Scholar
  71. Wiebecke, B., Krey, U., Löhrs, U., and Eder, M., 1973, Morphological and autoradiographical investigations on experimental carcinogenesis and polyp development in the intestinal tract of rats and mice, Virchows Arch. Pathol. Anat. 360: 179–193.CrossRefGoogle Scholar
  72. Zedeck, M. S., Sternberg, S. S., Poynter, R. W., and McGowan, J., 1970, Biochemical and pathological effects of methylazoxymethanol acetate, a potent carcinogen, Cancer Res. 30: 801–812.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • Alain P. Maskens
    • 1
  1. 1.Cancer Research UnitClinique Saint-MichelBrusselsBelgium

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