Abstract
There is a longstanding debate in cancer research about the primary cause of malignant cell growth: is cancer the result of genetic events or the outcome of epigenetic processes? The weight of opinion seems to shift with research trends of biology in general. It is, of course, central to the resolution of such a problem that the concepts at issue be defined. Genetic events are of two basic kinds, mutation and chromosome recombination. Mutations result from a change in the sequence of nucleotides in DNA. They are generally assumed to occur at random with a frequency of less than 10−6 per cell division with little or no evidence of specificity1. Chromosome recombination normally occurs in an orderly way in sexual reproduction. It also occurs in disorderly fashion in somatic cells of aging individuals2,3, in tumors4,5 and in cell culture6,7. Except for certain leukemias8, abnormalities in cell chromosome structure or number in common adult cancers show little evidence of a specific causal relation to the origin of the tumor. However, genetic change is conceptually simple and has been vigorously analyzed in this area of molecular biology. Concurrently, there has been a strong shift toward acceptance of genetic change in somatic cells as the cause of most cancers, and at least part of this shift stems from the combination of conceptual simplicity plus the availability of a highly developed molecular technology for genetic analysis.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Abbreviations
- MCDB 402:
-
molecular, cellular and developmental biology medium 402
- CS:
-
calf serum
- FBS:
-
fetal bovine serum
References
T. T. Puck, Roundtable: Definition of criteria to define a genetic event, in: “Banbury Report 2. Mammalian Mutagenesis: The Maturation of Test Systems,” Cold Spring Harbor Laboratory, Cold Spring Harbor (1979).
P. A. Jacobs, M. Brunton, W. M. Court Brown, R. Doll, and R. Goldstein, Change of human chromosome count distributions with age: Evidence for a sex difference, Nature 197:1080–1081 (1963).
D. T. Hughes, Cytogenetical polymorphism and evolution in mammalian somatic cell populations in vivo and in vitro, Nature 217:518–523 (1968).
J. R. Shapiro, W.-K. A. Yung, and W. R. Shapiro, Isolatin, karyotype and clonal growth of heterogeneous subpopulations of human malignant gliomas, Cancer Res. 41:2349–2359 (1981).
S. R. Wolman, T. F. Phillips, and F. F. Becker, Fluorescent banding patterns of rat chromosomes in normal cells and primary hepatocellular carcinomas, Science 175:1267–1269 (1972).
M. Terzi, Chromosomal variation and the establishment of somatic cell lines in vitro, Nature 253:361–362 (1975).
L. S. Cram, M. F. Bartholdi, A. F. Ray, G. L. Travis, and P. M. Kraemer, Spontaneous neoplastic evolution of Chinese hamster cells in culture: Multistep progression of karyotype, Cancer Res. 43:4828–4837 (1983).
J. D. Rowley, Biological implications of consistent chromosomal rearrangements in leukemia and lymphoma, Cancer Res. 44:3159–3168 (1984).
C. H. Waddington, “The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology”, Allen and Unwin, London (1957).
D. L. Nanney, Epigenetic control systems, Proc. Natl. Acad. Sci. USA 44:712–717 (1958).
D. L. Nanney, Molecules and morphologies: The perpetuation of pattern in the ciliated protozoa, J. Protozool. 24:27–35 (1977).
D. A. Clayton, Transcription of the mammalian mitochondrial genome, Ann. Rev. Biochem. 53:573–594 (1984).
T. J. King and R. Briggs, Serial transplantation of embryonic nuclei, Cold Spring Harbor Symposia Quant. Biol. 21:271–290 (1956).
H. E. Varmus, The molecular genetics of cellular oncogenes, Ann. Rev. Genet. 18:553–612 (1984).
S. Mondai and C. Heidelberger, In vitro malignant transformation by methylcholanthrene of the progeny of single cells derived from C3H mouse prostate, Proc. Natl. Acad. Sci. USA 65:219–229 (1970).
A. R. Kennedy, M. Fox, G. Murphy, and J. B. Little, Relationship between X-ray exposure and malignant transformation in C3H 10T1/2 cells, Proc. Natl. Acad. Sci. USA 77:7262–7266 (1980).
A. R. Kennedy, J. Cairns, and J. B. Little, Timing of the steps in transformation of C3H 10T1/2 cells by x-irradiation, Nature 307:85–86 (1984).
F. Seilern-Aspang and K. Kratochwil, Relation between regeneration and tumor growth, in: “Regeneration in Animals and Related Problems,” V. Kiortsis and H. Trampusch, eds., North Holland, Amsterdam (1965).
B. Mintz and K. Illmensee, Normal genetically mosaic mice produced from malignant teratocarcinoma cells, Proc. Natl. Acad. Sci. USA 72:3585–3589 (1975).
M. Oshimura, D. J. Fitzgerald, H. Kitamura, P. Nettesheim, and J. C. Barrett, Cytogenetic changes in rat tracheal epithelial cells during early stages of carcinogen-induced neoplastic progression, Cancer Res. 48:702–708 (1988).
J. L. Jainchill, S. A. Aaronson, and G. J. Todaro, Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells, J. Virol. 4:549–553 (1969).
G. D. Shipley and R. G. Ham, Attachment and growth of Swiss and Balb/c 3T3 cells in a completely serum-free medium, In Vitro 16:218 (1980).
H. Rubin, B. M. Chu, and P. Arnstein, Dynamics of tumor growth and cellular adaptation after inoculation into nude mice of varying number of transformed 3T3 cells and of readaptation to culture of the tumor cells, Cancer Res. 46:2027–2034 (1986).
T. Gurney, Local stimulation of growth in primary cultures of chick embryo fibroblasts, Proc. Natl. Acad. Sci. USA 62:906–911 (1969).
R. Fleischmajer and R. E. Billingham, eds. “Epithelial-Mesenchymal Interactions,” The Williams and Wilkins Company, Baltimore (1968).
R. E. Scott, B. J. Hoerl, J. J. Wille, Jr., D. L. Florine, B. R. Krawisz, and K. Yun, Coupling of proadipocyte growth arrest and differentiation II. A cell cycle model for the physiological control of cell proliferation, J. Cell. Biol. 94:400–405 (1982).
D. I. DePomerai, F.-H. Kotecha, C. Fullick, A. Young, and M. A. H. Gali, Expression of differentiation markers by chick embryo neuroretinal cells in vivo and in culture, J. Embryol. Exp. Morph. 77:201–220 (1983).
P. R. Cline and R. H. Rice, Modulation of involucrin and envelope competence in human keratinocytes by hydrocortisone, retinyl acetate and growth arrest, Cancer Res. 43:3203–3207 (1983).
D. A. Haber, D. A. Fox, W. S. Dynan, and W. G. Thilly, Cell density dependence of focus formation in the C3H 10T1/2 transformation assay, Cancer Res. 37:1644–1648 (1982).
J. S. Bertram, Effects of serum concentration on the expression of carcinogen-induced transformation in the C3H/10T1/2 CL8 cell line, Cancer Res. 37:514–523 (1977).
W. F. Benedict, W. L. Wheatley, and P. A. Jones, Inhibition of chemically induced morphological transformation and reversion of the transformed phenotype by ascorbic acid in C3H 10T1/2 cells, Cancer Res. 40:2796–2801 (1980).
E. Farber, Pre-cancerous steps in carcinogenesis: Their physiological adaptive nature, Biochim. Biophys. Acta 738:171–180 (1984).
E. Farber and D. S. R. Sarma, Biology of disease. Hepatocarcinogenesis: A dynamic cellular perspective, Lab. Invest. 56:4–22 (1987).
D. G. Blair, C. S. Cooper, M. K. Oskarsson, L. A. Eader, and G. F. Vande Woude, New method for detecting cellular transforming genes, Science 218:1122–1124 (1982).
M. A. Tainsky, F. L. Shamansky, D. Blair, and G. Vande Woude, Human recipient cell for oncogene transfection studies, Mol. Cell. Biol. 7:1280–1284 (1987).
R. G. Greig, T. P. Koestler, D. L. Trainer, S. P. Corwin, L. Miles, T. Kline, R. Sweet, S. Yokoyama, and G. Poste, Tumorigenic and metastatic properties of “normal” and ras-transformed NIH 3T3 cells, Proc. Natl. Acad. Sci. USA 82:3698–3701 (1985).
W. M. Elsasser, Reflections on a theory of organisms, Éditions Orbis Publishing, Frelighsburg (1987).
A. Eddington, “The Philosophy of Science,” reprinted by the University of Michigan Press, Ann Arbor (1939).
Science, 188:68-70 (1975).
Cancer Res. 36:1626-1633, (1976).
J. Supramolecular Structure 5:131-137 (1976).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Rubin, H., Xu, K. (1991). Epigenetic Features of Spontaneous Transformation in the NIH 3T3 Line of Mouse Cells. In: Sudilovsky, O., Pitot, H.C., Liotta, L.A. (eds) Boundaries between Promotion and Progression during Carcinogenesis. Basic Life Sciences, vol 57. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5994-4_25
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5994-4_25
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5996-8
Online ISBN: 978-1-4684-5994-4
eBook Packages: Springer Book Archive