Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1989 Jul;80(7):599–607. doi: 10.1111/j.1349-7006.1989.tb01683.x

Progression: The Terminal Stage in Carcinogenesis

Henry C Pitot 1
PMCID: PMC5917813  PMID: 2507482

Full Text

The Full Text of this article is available as a PDF (641.9 KB).

REFERENCES

  • 1. ) Rous , P. and Kidd , J. G.Conditional neoplasms and sub‐threshold neoplastic states: a study of the tar tumors of rabbits . J. Exp. Med. , 73 , 369 – 390 ( 1941. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) Mottram , J. C.A developing foctor in experimental blastogenesis . J. Pathol. Bacteriol. , 56 , 181 – 187 ( 1944. ). [Google Scholar]
  • 3. ) Berenblum , I. and Shubik , P.A new quantitative approach to the study of stages of chemical carcinogenesis in the mouse's skin . Br. J. Cancer , 1 , 383 ( 1947. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. ) Foulds , L.The experimental study of tumor progression: a review . Cancer Res. , 14 , 327 – 339 ( 1954. ). [PubMed] [Google Scholar]
  • 5. ) Pitot , H. C.The stages in neoplastic development . In “ Cancer Epidemiology and Prevention, 2nd Ed. ,“ ed. Schottenfeld D. and Fraumeni J. , Oxford University Press; , London , in press . [Google Scholar]
  • 6. ) Hendrich , S. , Glauert , H. P. and Pitot , H. C.The phenotypic stability of altered hepatic foci: effects of withdrawal and subsequent readministration of phenobarbital . Carcinogenesis , 7 , 2041 – 2045 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Boutwell , R. K.Some biological aspects of skin carcinogenesis . Progr. Exp. Tumor Res. , 4 , 207 – 250 ( 1964. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Iversen , O. H.TPA (12‐O‐tetradecanoyI‐phorbol‐13‐acetate) as a carcinogen for mouse skin . Virchows Arch. [Cell Pathol.] , 49 , 129 – 135 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Scherer , E. and Emmelot , P.Kinetics of induction and growth of precancerous liver‐cell foci, and liver tumour formation by diethylnitrosamine in the rat . Eur. J. Cancer , 11 , 689 – 696 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Lutz , W. K. and Maier , P.Genotoxic and epigenetic chemical carcinogenesis: one process, different mechanisms . TIPS Rev. , 9 , 322 – 326 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Schulte‐Hermann , R. , Timmermann‐Trosiener , I. and Schuppler , J.Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds . Cancer Res. , 43 , 839 – 844 ( 1983. ). [PubMed] [Google Scholar]
  • 12. ) Ip , C. , Yip , P. and Bernardis , L. L.Role of prolactin in the promotion of dimethylbenz [a] anthracene‐induced mammary tumors by dietary fat . Cancer Res. , 40 , 374 – 378 ( 1980. ). [PubMed] [Google Scholar]
  • 13. ) Hendrich , S. , Glauert , H. P. and Pitot , H. C.Dietary effects on initiation and promotion of hepatocarcinogenesis in rat . J. Cancer Res. Clin. Oncol. , 114 , 149 – 157 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Goerttler , K. , Loehrke , H. , Hesse , B. and Schweizer , J.Skin tumor formation in the European hamster (Cricetus cricetus L.) after topical initiation with 7, 12‐dimethylbenz‐[a] anthracene (DMBA) and promotion with 12‐O‐tetra‐decanoylphorbol‐13‐acetate (TPA) . Carcinogenesis , 4 , 521 – 524 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Delia Porta , G. , Dragani , T. A. and Manenti , G.Two‐stage liver carcinogenesis in the mouse . Tax. Pathol. , 15 , 229 – 233 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Witschi , H. P.Promotion oflung tumors in mice . Environ. Health Perspect. , 50 , 267 – 273 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Cohen , S. M.Promotion in urinary bladder carcinogenesis . Environ. Health Perspect. , 50 , 51 – 59 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Hiasa , Y. , Ohshima , M. , Kitahori , Y. , Yuasa , T. , Fujita , T. and Iwata , C.Promoting effects of 3‐amino‐1,2,4‐triazole on the development of thyroid tumors in rats treated with N‐bis(2‐hydroxypropyl)nitrosamine . Carcinogenesis , 3 , 381 – 384 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Foulds , L.Multiple etiologic factors in neoplastic development . Cancer Res. , 25 , 1339 – 1347 ( 1965. ). [PubMed] [Google Scholar]
  • 20. ) Fisher , E. R. , Shoemaker , R. H. and Sabnis , A.Relationship of hyperplasia to cancer in 3‐methylcholanthrene‐induced mammary tumorigenesis . Lab. Invest. , 33 , 33 – 42 ( 1975. ). [PubMed] [Google Scholar]
  • 21. ) Bevacqua , S. J. , Greeff , C. W. and Hendrix , M. J. C.Cytogenetic evidence of gene amplification as a mechanism for tumor cell invasion . Somatic Cell Mol. Genet. , 14 , 83 – 91 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Nicolson , G. L.Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression . Cancer Res. , 47 , 1473 – 1487 ( 1987. ). [PubMed] [Google Scholar]
  • 23. ) Frost , P. , Kerbel , R. S. , Hunt , B. , Man , S. and Pathak , S.Selection of metastatic variants with identifiable karyotypic changes from a nonmetastatic murine tumor after treatment with 2′‐deoxy‐5‐azacytidine or hydroxy‐urea: implications for the mechanisms of tumor progression . Cancer Res. , 47 , 2690 – 2695 ( 1987. ). [PubMed] [Google Scholar]
  • 24. ) Wolman , S. R.Karyotypic progression in human tumors . Cancer Metastasis Rev. , 2 , 257 – 293 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Ritchie , A. C.The classification, morphology, and behaviour of tumours . In “ General Pathology ,“ ed. Florey H. W. , pp. 668 – 719 ( 1970. ). W. B. Saunders Co. , Philadelphia ). [Google Scholar]
  • 26. ) Nowell , P. C.Mechanisms of tumor progression . Cancer Res. , 46 , 2203 – 2207 ( 1986. ). [PubMed] [Google Scholar]
  • 27. ) Feinberg , A. P. and Coffey , D. S.The concept of DNA rearrangement in carcinogenesis and development of tumor cell heterogeneity . In “ Tumor Cell Heterogeneity ,” ed. Owens A. H. , Coffey D. S. and Baylin S. B. , pp. 469 – 494 ( 1982. ). Academic Press, Inc. , New York . [Google Scholar]
  • 28. ) Pitot , H. C. , Barsness , L. , Goldsworthy , T. and Kitagawa , T.Biochemical characterization of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine . Nature , 271 , 456 – 458 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Peraino , C. , Staffeldt , E. F. , Carnes , B. A. , Ludeman , V. A. , Blomquist , J. A. and Vesselinovitch , S. D.Characterization of histochemically detectable altered hepatocyte foci and their relationship to hepatic tumorigenesis in rats treated once with diethylnitrosamine or benzo[a]pyrene within one day after birth . Cancer Res. , 44 , 3340 – 3347 ( 1984. ). [PubMed] [Google Scholar]
  • 30. ) Eriksson , L. , Ahluwalia , M. , Spiewak , J. , Lee , G. , Sarma , D. S. R. , Roomi , M. J. and Farber , E.Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis . Environ. Health Perspect. , 49 , 171 – 174 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. ) Aldaz , C. M. , Conti , C. J. , Klein‐Szanto , A. J. P. and Slaga , T. J.Progressive dysplasia and aneuploidy are hallmarks of mouse skin papillomas: relevance to malignancy . Proc. Natl. Acad. Sci. USA , 84 , 2029 – 2032 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. ) Yoshida , T. H.Karyotype evolution and tumor development . Cancer Genet. Cytogenet. , 8 , 153 – 179 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 33. ) Pierce , G. B. and Speers , W. C.Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation . Cancer Res. , 48 , 1996 – 2004 ( 1988. ). [PubMed] [Google Scholar]
  • 34. ) Boveri , T. “ Zur Frage der Entstehung maligner Tumoren “ ( 1914. ). Gustav Fischer; , Jena ). [Google Scholar]
  • 35. ) Yunis , J. J.The chromosomal basis of human neoplasia . Science , 221 , 227 – 236 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 36. ) Yunis , J. J. , Bloomfield , C. D. and Ensrud , K.All patients with acute nonlymphocytic leukemia may have a chromosomal defect . N. Engl. J. Med. , 305 , 135 – 139 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 37. ) Wolman , S. R. , Horland , A. A. and Becker , F. F.Altered karyotypes of transplantable “diploid” tumors . J. Natl. Cancer Inst. , 51 , 1909 – 1914 ( 1973. ). [DOI] [PubMed] [Google Scholar]
  • 38. ) Sargent , L. , Xu , Y‐H. , Sattler , G. L. and Pitot , H. C.Ploidy and karyotype of hepatocytes isolated from enzyme‐altered foci in two different protocols of multistage hepatocarcinogenesis in the rat . Carcinogenesis , 10 , 387 – 391 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 39. ) Solt , D. and Farber , E.New principle for the analysis of chemical carcinogenesis . Nature , 263 , 701 – 703 ( 1976. ). [Google Scholar]
  • 40. ) Préat , V. , de Gerlache , J. , Lans , M , Taper , H. and Roberfroid , M.Comparative analysis of the effect of phenobarbital, dichlorodiphenyltrichloroethane, butylated hydroxytoluene and nafenopin on rat hepatocarcinogenesis . Carcinogenesis , 7 , 1025 – 1028 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 41. ) Nowell , P. C. and Morris , H. P.Chromosomes of “minimal deviation” hepatomas: a further report on diploid tumors . Cancer Res. , 29 , 969 – 970 ( 1969. ). [PubMed] [Google Scholar]
  • 42. ) Noweil , P. C.Genetic instability in cancer cells: relationship to tumor cell heterogeneity . In “ Tumor Cell Heterogeneity ,” ed. Owens A. H. , Coffey D. S. and Baylin S. B. , pp. 351 – 365 ( 1982. ). Academic Press, Inc. , New York . [Google Scholar]
  • 43. ) Sager , R. , Gadi , I. K. , Stephens , L. and Grabowy , C. T.Gene amplification: an example of accelerated evolution in tumorigenic cells . Proc. Natl. Acad. Sci. USA , 82 , 7015 – 7019 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. ) Chorazy , M.Sequence rearrangements and genome instability . J. Cancer Res. Clin. Oncol. , 109 , 159 – 172 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 45. ) Welch , D. R. and Tomasovic , S. P.Implications of tumor progression on clinical oncology . Clin. Exp. Metastasis , 3 , 151 – 188 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 46. ) Pitot , H. C.Oncogenes and human neoplasia . Clin. Lab. Med. , 6 , 167 – 179 ( 1986. ). [PubMed] [Google Scholar]
  • 47. ) Klein , G. and Klein , E.Conditioned tumorigenicity of activated oncogenes . Cancer Res. , 46 , 3211 – 3224 ( 1986. ). [PubMed] [Google Scholar]
  • 48. ) Parker , M. G. and Page , M. J.Use of gene transfer to study expression of steroid‐responsive genes . Mol. Cell. Endocrinol. , 34 , 159 – 168 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 49. ) Pitot , H. C. “ Fundamentals of Oncology, 3rd Ed. “ ( 1986. ). Marcel Dekker, Inc. , New York . [Google Scholar]
  • 50. ) Pitot , H. C. , Beer , D. and Hendrich , S.Multistage carcinogenesis: the phenomenon underlying the theories . In “ Theories of Carcinogenesis ,“ ed. Iversen O. , pp. 159 – 177 ( 1988. ). Hemisphere Press; , Washington ). [Google Scholar]
  • 51. ) Sinha , A. A.Hormone sensitivity and autonomy of tumours . In “ Hormonal Management of Endocrine‐related Cancer ,“ ed. Stoll B. A. , pp. 13 – 19 ( 1981. ). Lloyd‐Luke, Ltd. , London . [Google Scholar]
  • 52. ) Cedar , H.DNA methylation and gene activity . Cell , 53 , 3 – 4 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 53. ) Babiss , L. E. , Zimmer , S. G. and Fisher , P. B.Reversibility of progression of the transformed phenotype in Ad 5‐transformed rat embryo cells . Science , 228 , 1099 – 1101 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 54. ) Kerbel , R. S. , Frost , P. , Liteplo , R. , Carlow , D. A. and Elliott , B. E.Possible epigenetic mechanisms of tumor progression: induction of high‐frequency heritable but phenotypically unstable changes in the tumorigenic and metastatic properties of tumor cell populations by 5‐azacytidine treatment . J. Cell. Physiol. Suppl. , 3 , 87 – 97 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 55. ) Goldsworthy , T. L. , Hanigan , M. H. and Pitot , H. C.Models of hepatocarcinogenesis in the rat — contrasts and comparisons . CRC Crit. Rev. Toxicol. , 17 , 61 – 89 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 56. ) Wigley , C. B.Experimental approaches to the analysis of precancer . Cancer Sun. , 2 , 495 – 515 ( 1983. ). [Google Scholar]
  • 57. ) Lin , D. Y. , Liaw , Y‐F. , Chu , C. M. , Chang‐Chien , C. S. , Wu , C. S. , Chen , P. C. and Sheen , I. S. , Hepatocellular carcinoma in noncirrhotic patients . Cancer , 54 , 1466 – 1468 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 58. ) Kuramoto , S. and Oohara , T.Minute cancers arising de nova in the human large intestine . Cancer , 61 , 829 – 834 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 59. ) Williams , G. M.The pathogenesis of rat liver cancer caused by chemical carcinogens . Biochim. Biophys. Acta , 605 , 167 – 189 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 60. ) Maskens , A. P. and Dujardin‐Loits , R. M.Experimental adenomas and carcinomas of the large intestine behave as distinct entities: most carcinomas arise de novo in flat mucosa . Cancer , 47 , 81 – 89 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 61. ) Christopherson , W. M.Dysplasia, carcinoma in situ, and microinvasive carcinoma of the uterine cervix . Hum. Pathol. , 8 , 489 – 501 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 62. ) Day , D. W.The adenoma‐carcinoma sequence . Scand. J. Gastroenterol. , 19 ( suppl. ) 104 , 99 – 107 ( 1984. ). [PubMed] [Google Scholar]
  • 63. ) Scherer , E.Relationship among histochemically distinguishable early lesions in multistep‐multistage hepatocarcinogenesis . Arch. Toxicol. Suppl. , 10 , 81 – 94 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 64. ) Hermanek , P. J. and Giedl , J.The adenoma‐carcinoma sequence in AMMN‐induced colonic tumors of the rat . Pathol. Res. Pract. , 178 , 548 – 554 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 65. ) Pitot , H. C.Characterization of the stage of progression in hepatocarcinogenesis in the rat . In “ Boundaries between Promotion and Progression ,“ ed. Sudilovsky O. , Liotta L. and Pitot H. C. , Plenum Publishing Corp. , New York , in press . [Google Scholar]
  • 66. ) Potter , V. R.A new protocol and its rationale for the study of initiation and promotion of carcinogenesis in rat liver . Carcinogenesis , 2 , 1375 – 1379 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 67. ) Campbell , H. A. , Xu , Y. D. , Hanigan , M. H. and Pitot , H. C.Application of quantitative stereology to the evaluation of phenotypically heterogeneous enzyme‐altered foci in the rat liver . J. Natl. Cancer Inst. , 76 , 751 – 767 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 68. ) O'Connell , J. F. , Klein‐Szanto , A. J. P. , DiGiovanni , D. M. , Fries , J. W. and Slaga , T. J.Enhanced malignant progression of mouse skin tumors by the free‐radical generator benzoyl peroxide . Cancer Res. , 46 , 2863 – 2865 ( 1986. ). [PubMed] [Google Scholar]
  • 69. ) Hennings , H. , Shores , R. , Wenk , M. L. , Spangler , E. F. , Tarone , R. and Yuspa , S. H.Malignant conversion of mouse skin tumours is increased by tumour initiators and unaffected by tumour promoters . Nature , 304 , 67 – 69 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 70. ) O'Connell , J. F. , Klein‐Szanto , A. J. P. , DiGiovanni , D. M. , Fries , J. W. and Slaga , T. J.Malignant progression of mouse skin papillomas treated with ethylnitrosourea, N‐methyl‐N‐nitro‐N‐nitrosoguanidine, or 12 ‐O‐tetradeca‐noylphorbol‐13‐acetate . Cancer Lett. , 30 , 269 – 274 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 71. ) Rotstein , J. B. and Slaga , T. J.Acetic acid, a potent agent of tumor progression in the multistage mouse skin model for chemical carcinogenesis . Cancer Lett. , 42 , 87 – 90 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 72. ) Peraino , C. , Staffeldt , E. F. and Ludeman , V. A.Early appearance of histochemically altered hepatocyte foci and liver tumors in female rats treated with carcinogens one day after birth . Carcinogenesis , 2 , 463 – 465 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 73. ) Pitot , H. C. , Barsness , L. , Goldsworthy , T. and Kitagawa , T.Biochemical characterization of stages of hepatocarci‐nogenesis after a single dose of diethylnitrosamine . Nature , 271 , 456 – 458 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 74. ) Balmain , A. , Ramsden , M. , Bowden , G. T. and Smith , J.Activation of the mouse cellular Harvey‐ ras gene in chemically induced benign skin papillomas . Nature , 307 , 658 – 660 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 75. ) Reynolds , S. H. , Stowers , S. J. , Maronpot , R. R. , Anderson , M. W. and Aaronson , S. A.Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse . Proc. Natl. Acad. Sci. USA , 83 , 33 – 37 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76. ) Guillem , J. G , Hsieh , L. L. , O'Toole , K. M. , Forde , K. A. , LoGerfo , P. and Weinstein , I. B.Changes in expression of oncogenes and endogenous retroviral‐like sequences during colon carcinogenesis . Cancer Res. , 48 , 3964 – 3971 ( 1988. ). [PubMed] [Google Scholar]
  • 77. ) Erisman , M. D. , Rothberg , P. G. , Diehl , R. E. , Morse , C. C. , Spandorfer , J. M. and Astrin , S. M.Deregulation of c‐myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene . Mol. Cell Biol. , 5 , 1969 – 1976 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78. ) Tanaka , T. , Slamon , D. J. , Battifora , H. and Cline , M. J.Expression of p21 ras oncoproteins in human cancers , Cancer Res. , 46 , 1465 – 1470 ( 1986. ). [PubMed] [Google Scholar]
  • 79. ) Galand , P. , Jacobovitz , D. and Alexandre , K.Immunohistochemical detection of c‐Ha‐ras oncogene p21 product in pre‐neoplastic and neoplastic lesions during hepatocarcinogenesis in rats . Int. J. Cancer , 41 , 155 – 161 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 80. ) Ito , S. , Watanabe , T. , Abe , K. , Yanaihara , N. , Tateno , C. , Okuno , Y. , Yoshitake , A. and Miyamoto , J.Im‐munohistochemical demonstration of the c‐myc oncogene product in rat chemical hepatocarcinogenesis . Biomed. Res. , 9 , 177 – 180 ( 1988. ). [Google Scholar]
  • 81. ) Nagy , P. , Evarts , R. P. , Marsden , E. , Roach , J. and Thorgeirsson , S. S.Cellular distribution of c‐myc transcripts during chemical hepatocarcinogenesis in rats . Cancer Res. , 48 , 5522 – 5527 ( 1988. ). [PubMed] [Google Scholar]
  • 82. ) Richmond , R. E. , Pereira , M. A. , Carter , J. A. , Carter , H. W , and Long , R. E.Quantitative and qualitative im‐munohistochemical detection of myc and src oncogene proteins in normal, nodule, and neoplastic rat liver . J. Histochem, Cytochem. , 36 , 179 – 184 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 83. ) Cote , G. J. , Lastra , B. A. , Cook , J. R. , Huang , D‐P. and Chiu , J. F.Oncogene expression in rat hepatomas and during hepatocarcinogenesis . Cancer Lett. , 26 , 121 – 127 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 84. ) Makino , R. , Hayashi , K. , Sato , S. and Sugimura , T.Expressions of the c‐Ha‐ras and c‐myc genes in rat liver tumors . Biochem. Biophys. Res. Commun. , 119 , 1096 – 1102 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 85. ) Beer , D. G. , Schwarz , M. , Sawada , N. and Pitot , H. C.Expression of H‐ras and c‐myc protooncogenes in isolated γ‐glutamyl transpeptidase‐positive rat hepatocytes and in hepatocellular carcinomas induced by diethylnitrosamine . Cancer Res. , 46 , 2435 – 2441 ( 1986. ). [PubMed] [Google Scholar]
  • 86. ) Knudson , A. G. , Jr.Genetics and the etiology of childhood cancer . Pediat. Res. , 10 , 513 – 517 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 87. ) Thomassen , D. G. , Gilmer , T. M. , Annab , L. A. and Barrett , J. C.Evidence for multiple steps in neoplastic transformation of normal and preneoplastic Syrian hamster embryo cells following transfection with Harvey murine sarcoma virus oncogene (v‐Ha‐ras) . Cancer Res. , 45 , 726 – 732 ( 1985. ). [PubMed] [Google Scholar]
  • 88. ) Land , H. , Parada , L. F. and Weinberg , R. A.Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes . Nature , 304 , 596 – 602 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 89. ) Hansen , M. F. and Cavenee , W. K.Genetics of cancer predisposition . Cancer Res. , 47 , 5518 – 5527 ( 1987. ). [PubMed] [Google Scholar]
  • 90. ) Saeter , G. , Schwarze , P. E. , Nesland , J. M. , Juul , N. , Pettersen , E. O. and Seglen , P. O.The polyploidizing growth pattern of normal rat liver is replaced by divisional, diploid growth in hepatocellular nodules and carcinomas . Carcinogenesis , 9 , 939 – 945 ( 1988. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES