Summary
The integrity of the DNA of each cell is necessary for normal functioning of the cell and the organism. DNA damage, if not repaired, might influence the expression of genes in that cell, as well as act as cytotoxic and mutagenic substrates. Genetic, developmental, physiological, nutritional and environmental factors are known to influence both the amount and kind of DNA damage, as well as its repair. Not all gene or chromosomal mutations are the result of agents which damage DNA. Factors which could alter the fidelity of DNA replication of normal DNA templates, as well as the segregation of chromosomes, could lead to both gene and chromosomal mutations. Since carcinogenesis is a multi-step process, involving the transformation of a normal cell to a premalignant cell, with subsequent clonal expansion and phenotypic evolution of that premalignant cell to a malignant cell, DNA damage and faulty DNA repair probably play a significant role in carcinogenesis through the production of mutations and cell killing. Cell killing due to inadequate DNA repair of DNA damage (or due to any other means) could act as a mitogenic stimulus by inducing regenerative hyperplasia. This hyperplasia stimulus, by amplifying initiated cells and creating opportunities for other unrepaired DNA lesions to be substrates for new mutations during cell division, might be responsible for converting the prenmalignant cell to the malignant cell, thus completing the carcinogenic process. Inhibition of intercellular communication by a wide cariety of physical, chemical and biological factors has been postulated to disrupt the regulation of proliferation and differentiation in stem cells. Agents which interrupt intercellular communication during early organogenesis have the potential to be teratogens, while if they are present in the developed, initiated organism they have the potential to be tumor promoters. Consequently, the observed linkage between teratogens and carcinogens might be mediated by their ability, via several mechanisms, to interfere with intercellular communication.
Research was supported by granst to J. E. T. from the National Cancer Institute (CA 21104, CA 26803) and the EPA (R808587010).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Amed, F. E. , and R. B. Setlow (1978) Excision repair in ataxia langiectasia, Fanconi’s anemia, Cockayne syndrome and Bloom’s syndrome after treatment with ultraviolet radiation and N-acetoxy-2-acetylamino-fluorene.Biochim. Biophys. Acta521: 805 – 817.
Ashley, D. J. (1969) The two “hit” and multiple “hit” theories of carcinogenesis.Br. J. Cancer23: 313 - 328.
Berenblum, I. , and P. Shubik (1947) A new, guantitative approach to the study of the stages of chemical carcinogenesis in the mouse’s skin.Br. J. Cancer1: 383 – 391.
Bonaiti-Pellie, C. , M. L. , Briard-Guillemot, J. Feingold, and J. Frezal (1975) Associated congenital malformations in retinoblastoma.Clinical Genetics7: 37 – 39.
Cairns, J. (1981) The origin of human cancers.Nature289: 353 – 357.
Collet, M. S. , and R. L. Erikson (1978) Protein kinase activity associated with the avian sarcoma virus Src gene product.Proc. Natl. Acad. Sci. USA75: 2021 – 2024.
Corsaro, C. M. , and B. R. Migeon (1977) Comparison of contact- mediated communication in normal and transformed human cells in culture.Proc. Natl. Acad. Sci. USA74: 4476 – 4480.
Diamond, L. , T. G. O’Brien, and G. Rovera (1978) Tumor promoters: Effects on proliferation and differentiation of cells in culture.Life Science23: 1979 – 1988.
Edelman, G. M. (1983) Gell adhesion molecules.Science219: 450 – 457.
Elias, P. M. , S. Grayson, I. M. Caldwell, and N. S. McNutt (1980) Gap junction proliferation in retinoic acid-treated human basal cell carcinoma.Lab. Invest. 42: 469 – 474.
Emerit, I. , and P. Cerutti (1981) Clastogenic activity from Bloom’s syndrome fibroblast cultures.Proc. Natl. Acad. Sci. USA78: 1868 - 1872.
Fialkow, P. J. (1976) Clonal origin of human tumors.Biochim. Biophys. Acta458: 384 – 421.
Flagg-Newton, J. L. , G. Dahl, and W. R. Loewenstein (1981) Cell junction and cyclic AMP: 1. Upregulation of junctional and membrane permeability and junctional membrane particles by administration of cyclic nucleotide or phosphodiesterase inhibitor.J. Memb. Biol. 63: 105 – 121.
Foulds, L. (1954) The experimental study of tumor progression: A review.Cancer Res. 14: 327 – 339.
Freese, E. (1982) Use of cultured cells in the identification of potential teratogens.Teratogenesis, Carcinogenesis and Mutagenesis2: 355 – 360.
German, J. , D. Bloom, and E. Passarge (1977) Bloom’s syndrome, V. Surveillance for cancer in affected families.Clin. Genet. 12: 162 – 168.
Hanigan, H. M. , and H. C. Pitot (1982) Isolation of oc-glutamyl transpeptidase positive hepatocytes during the early stages of hepatocarcinogenesis in the rat.Carcinogenesis3: 1349 – 1354.
Hand, R. , and J. German (1975) A retarded rate of DNA chain grcwth in Bloom’s syndrome.Proc. Natl. Acad. Sci. USA72: 758 – 762.
Harbison, R. D. (1978) Chemical-biological reactions common to teratogenesis and mutagenesis.Env. Health Persp. 24: 87 – 100.
Hirata, F. , and J. Axelrod (1980) Phospholipid methylation and biological signal transmission.Science209: 1082 – 1090.
Hiwasa, T. , S. Fujimara, and S. Sakiyama (1982) Tumor promoters increase the synthesis of a 32,000 dalton protein in BALB/c 3T3 cells.Proc. Natl. Acad. Sci. USA79: 1800 – 1804.
Houston, E. W. , W. C. Levin, and S. E. Ritzmann (1964) Endoreduplication in untreated early leukemia.Lancetii: 496 – 497.
Huang, Y. , C. C. Chang, and J. E. Trosko (1983) Aphidicolin induces endoreduplication in Chinese hamster cells.Cancer Res. 43: 1361 – 1364.
Huang, Y. , C. C. Chang, and J. E. Trosko (1983) Aphidicolin induces endoreduplication in Chinese hamster cells.Cancer Res. 43: 1361 – 1364.
Jensen, R. K. , S. D. Sleight, J. I. Goodman, S. D. Aust, and J. E. Trosko (1982) Polybrominated biphenyls as promoters in experimental hepatocarcinogenesis in rats.Carcinogenesis3: 1183 – 1186.
Johnson, E. M. (1980) Screening for teratogenic potential: Are we asking the proper question?Teratology21: 259.
Kano, Y. , and Y. Fujiwara (1982) Higher induction of twin and single sister chromatid exchanges by cross-linking agents in Fanconi’s anemia cells.Human Genet. 60: 233 – 238.
Keijzer, W. , N. G. J. Jaspers, P. J. Abrahams, A. M. R. Taylor, C. F. Arlett, B. Zelle, H. Takebe, P. D. S. Kinmont, and D. Bootsma (1979) A seventh complementation group in excision-deficient xeroderma pigmentosum.Mutat. Res. 62: 183 – 190.
Knudson, A. G. (1971) Mutation and cancer: Statistical study of retinoblastoma.Proc. Natl. Acad. Sci. USA68: 820 - 823.
Knudson, A. G. , Jr. (1977) Genetic predisposition to cancer, InOrigins of Human Cancer, H. H. Hiatt, J. D. Watson, and J. A. Winsten, Eds. , Cold Spring Harbor Laboratory, New York, pp. 45 – 52.
Konze-Thomas, B. , R. M. Hazard, V. M. Maher, and J. J. McCormick (1982) Extent of excision repair before DNA synthesis determines the mutagenic but not the lethal effect of UV- radiation.Mut. Res. 94: 421 – 434.
Koyabyashi, N. , T. Furukawa, and T. Takatsu (1968) Congenital anomalies in children with malignancy.Pediatr. Univ. Tokyo16: 31 – 37.
Kraemer, K. H. (1980) Oculo-cutaneous and internal neoplasms in xeroderma pigmentosum: Implications for theories of carcinogenesis, InCarcinogenesis: Fundamental Mechanisms and Environmental Effects, B. Pullman, P. O. P. Tfso, and H. Gelboin, Eds. , D. Reidel, Amsterdam, pp. 503 – 507.
Kunz, B. A. (1982) Genetic effects of deoxyribonucleotide pool imbalances.Environ. Mut. 4: 695 – 725.
Lechner, J. F. , and H. E. Kaighn (1980) EGF growth promoting activity is neutralized by phorbol esters.Cell Biology Intern. Reports4: 23 – 28.
Li, F. P. (1978) Host factors in childhood cancers.Semin. Oncol. 5: 17 – 23.
Little, J. B. (1977) Radiation carcinogenesis in vitro: Implications for mechanisms, InOrigins of Human Cancer, H. H. Hiatt, J. D. Vfetson, J. A. Winsten, Eds. , Cold Spring Harbor, New York, pp. 923 – 939.
Liu, P. K. , C. C. Chang, J. E. Trosko, D. K. Dube, G. M. Martin, and L. A. Loeb (1983) Mammalian mutator mutant with an aphidicolin-resistant DNA polymerase ac.Proc. Natl. Acad. Sci. USA80: 797 – 801.
Loewenstein, W. R. (1979) Junctional intercellular communication and the control of growth.Biochim. Biophys. Acta560: 1 – 65.
Lynch, H. T. , H. Guirgis, P. Lynch, J. Lynch, and R. Harris (1977) Familial cancer syndromes: A survey.Cancer39: 1867 – 1868.
MacDonald, C. (1982) Genetic complementation in hybrid cells derived from two metabolic cooperation defective mammalian cell lines.Exp. Cell Res. 738: 303 – 310.
Maden, M. (1982) Vitamin A and pattern formation in the regenerating limb. Nature 295: 672 – 675.
Maher, V. M. , and J. J. McCormick (1976) Effect of DNA repair on the cytotoxicity and mutagenicity of UV-irradiation of chemical carcinogens in normal and xeroderma pigmentosum cells, InBiology of Radiation Carcinogenesis, J. M. Yahus, R. W. Tennent, and J. D. Regan, Eds. , Raven Press, New York, pp. 129 – 145.
Maroun, L. E. (1980) Interferon action and chromosome 21 trisomy.J. Theoret. Biol. 86: 603 - 606.
Miller, J. A. , and E. C. Miller (1977) Ultimate chemical carcinogens as reactive mutagenic electrophiles, InOrigins of Human Cancer, Book B, H. H. Hiatt, J. D. Vfetson, and J. A. Winsten, Eds. , Cold Spring Harbor Laboratory, New York, pp. 605 – 627.
Miller, M. R. , and D. N. Chinault (1982) Evidence that DNA polymerases oc and £ participate differentially in DNA repair synthesis induced by different agents.J. Biol. Chem. 257: 46 - 49.
Miller, R. W. (1977) Relationship between human teratogens and carcinogens.J. Nat. Cancer Inst. 58: 471 – 474.
Mulvihill, J. J. (1975) Congenital and genetic diseases, InPersons at High Risk of Cancer, J. F. Fraumeni, Ed. , Academic Press, New York, pp. 3 – 37.
Nakamo, S. , H. Yamagami, and R. Takaki (1979) Enhancement of excision-repair efficiency by conditioned medium from density-inhibited cultures in V79 Chinese hamster cells.Mut. Res. 62: 369 – 381.
Niedel, J. E. , L. J. Kuhn, and G. R. Vanderbark (1983) Phorbol diester receptor copurifies with protein kinase.Proc. Natl. Acad. Sci. USA80: 36 – 40.
Owens, A. H. , D. S. Coffey, and S. B. Baylin, Eds. (1982)Tumor Cell Heterogeneity, Academic Press, New York.
Pitot, H. C. , T. Goldsworthy, and S. Moran (1981) The natural history of carcinogenesis: Implications of experimental carcinogenesis in the genesis of human cancer.J. Supramolecular Struct. ’Cellul. Biochem. 17: 133 – 146.
Potter, V. R. (1978) Hormonal induction of enzyme functions, cyclic AMP levels and AIB transport in Morris hepatomas and in normal liver systems, InMorris Hepatomas: Mechanisms of Regulation, H. P. Morris, and W. E. Criss, Eds. , Plenum Press, New York, pp. 59 – 87.
Potter, V. R. (1980) Initiation and promotion in cancer formation: The importance of studies on intercellular communication.Yale J. Biol. Med. 53: 367 – 384.
Purtilo, D. T. , L. Paquin, and T. Gindhart (1978) Genetics of necplasia-impact of ecogenetics on oncogenesis.Amer. J. Pathol. 91: 609 – 681.
Reddy, E. P. , R. K. Reynolds, E. Santos, and M. Barbacid (1982) A point mutation is responsible for the acquisition of transforming properties fcy the T24 human bladder carcinoma oncogene.Nature300: 149 – 152.
Roth, R. A. , and D. J. Cassell (1983) Insulin receptor: Evidence that it is a protein kinase.Science219: 249 – 301.
Rcwley, J. D. (1983) Human oncogene locations and chromosome aberrations.Nature301: 290 – 291.
Simons, J. W. I. M. (1979) Development of a liquid holding technique for the study of DNA repair in human diploid fibroblasts.Mut. Res. 59: 273 – 283.
Spadari, S. , and A. Weissbach (1974) The inter-relations between DNA synthesis and various DNA polymerase activities in synchronized Hela cells.J. Mol. Biol. 86: 11 – 20.
Steinberg, M. , and V. Defendi (1981) Patterns of cell communication and differentiation in SV40 transformed human keratinocytes.J. Cell. Physiol. 109: 153 – 159.
Tabin, C. J. , S. M. Bradley, C. I. Bargmann, R. A. Weinberg, A. G. Papageorge, E. M. Scolnick, R. Dhar, D. R. Lcwy, and E. H. Chang (1982) Mechanism of activation of a human oncogene.Nature300: 143 – 149.
Trosko, J. E. (1981) Cancer causation. Nature 290: 356.
Trosko, J. E. , and C. C. Chang (1978) Environmental carcinogenesis: An integrative model.Quart. Rev. Biol. 53: 115 – 141.
Trosko, J. E. , and C. C. Chang (1979) Chemical carcinogenesis as a consequence of alterations in the structure and function of DNA, InChemical Carcinogens and DNA, Vol. II, CRC Press, Boca Raton, Florida, pp. 181 – 260.
Trosko, J. E. , and C. C. Chang (1981) An integrative hypothesis linking cancer, diabetes and atherosclerosis: The role of mutations and epigenetic changes.Med. Hypotheses6: 455 – 468.
Trosko, J. E. , and C. C. Chang (1981) The role of radiation and chemicals in the induction of mutations and epigenetic changes during carcinogenesis.Advances in Radiation Biology. Vol. 9, Academic Press, New York, pp. 1 – 36.
Trosko, J. E. , and C. C. Chang (1981) The role of radiation and chemicals in the induction of mutations and epigenetic changes during carcinogenesis.Advances in Radiation Biology. Vol. 9, Academic Press, New York, pp. 1 – 36.
Trosko, J. E. , C. C. Chang, and M. Netzloff (1982) The role of inhibited cell-cell communication in teratogenesis.Teratogenesis, Carcinogenesis and Mutagenesis2: 31 – 45.
Trosko, J. E. , C. Jone, and C. C. Chang (1983) The role of tumor promoters on phenotypic alterations affecting intercellular communication and tumorigenesis.New York Acad. Sci. 407: 316 – 327.
Trosko, J. E. , C. Jone, and C. C. Chang (1983) The role of tumor promoters on phenotypic alterations affecting intercellular communication and tumorigenesis.New York Acad. Sci. 407: 316 – 327.
Tsushimoto, G. , J. E. Trosko, C. C. Chang, and S. D. Aust (1982) Inhibition of metabolic cooperation in Chinese hamster V79 cells in culture by various polybrominated biphenyl (PBB) congeners.Carcinogenesis3: 181 – 186.
Warren, S. T. , R. A. Schultz, C. C. Chang, M. H. Wade, and J. E. Trosko (1981) Elevated spontaneous mutation rate in Bloom’s syndrome fibroblasts.Proc. Natl. Acad. Sci. USA78: 3133 – 3137.
Wawra, E. , and I. Dolejs (1979) Evidences for the function of DNA polymerase pin unscheduled DNA synthesis.Nucleic Acids Res. 7: 1675 – 1686.
Weinstein, I. B. , L. S. Lee, P. B. Fisher, A. Mufson, and H. Yamasaki (1979) Action of phorbol esters in cell culture: Mimicry of transformation altered differentiation and effects on cell membranes,J. Supramolecular Struct. 2: 194 – 208.
Welshimer, K. , and M. Swift (1982) Congenital malformations and developmental disabilities in ataxia telangiectasia, Fanconi’s anemia, and xeroderma pigmentosum families. Am.J. Hum. Genet. 34: 781 – 793.
Weymouth, L. A. , and L. A. Loeb (1978) Mutagenesis during in vitro DNA synthesis.Proc. Natl. Acad. Sci. USA75: 1924 – 1928.
Wilson, J. G. (1977) Current status of teratology, InHandbook of Teratology, J. G. Wilson and F. C. Fruser, Eds. , Plenum Press, New York, pp. 47 – 74.
Yager, J. D. , and R. Yager (1980) Oral contraceptive steroids as promoters of hepatocarcinogenesis in female Sprague-Dawley rats.Cancer Res. 40: 3680 – 3685.
Yancey, S. B. , J. E. Edens, C. C. Chang, and J. P. Revel (1982) Decreased incidence of gap junctions between Chinese hamster V79 cells upon exposure to the promoter, TP A. Expt. Cell Res, 139: 329 – 340.
Yotti, L. P. , C. C. Chang, and J. E. Trosko (1979) Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter. Science 206: 1089 – 1091.
Yotti, L. P. , T. W. Glover, J. E. Trosko, and D. J. Segal (1980) Comparative study of X-ray and UV-induced cytotoxicity, DNA repair and mutagenesis in Down’s syndrome and normal fibroblasts. Pediat. Res. 14: 88 – 92.
Yuspa, S. H. , T. Ben, H. Hennings, and U. Lichti (1982) Divergent responses in epidermal basal cells exposed to the tumor promoter 12-0-tetradecanoylphorbol-13-nacetate. Cancer Res. 42: 2344 – 2349.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1984 Plenum Press, New York
About this chapter
Cite this chapter
Trosko, J.E., Chang, Cc. (1984). A Possible Mechanistic Link between Teratogenesis and Carcinogenesis: Inhibited Intercellular Communication. In: Chu, E.H.Y., Generoso, W.M. (eds) Mutation, Cancer, and Malformation. Environmental Science Research, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2399-0_25
Download citation
DOI: https://doi.org/10.1007/978-1-4613-2399-0_25
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-9463-4
Online ISBN: 978-1-4613-2399-0
eBook Packages: Springer Book Archive