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Mutation, Cancer, and Malformation pp 529–547Cite as

A Possible Mechanistic Link between Teratogenesis and Carcinogenesis: Inhibited Intercellular Communication

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Part of the book series: Environmental Science Research ((ESRH,volume 31))

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).

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  1. Department of Pediatrics and Human Development, College of Human Medicine Michigan State University, East Lansing, MI, 48824-1317, USA

    James E. Trosko & Chia-cheng Chang

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  1. University of Michigan Medical School, Ann Harbor, Michigan, USA

    Ernest H. Y. Chu

  2. Oak Ridge National Laboratory, Oak Ridge, Tennesse, USA

    Walderico M. Generoso

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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

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