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Nongenotoxic Carcinogenesis pp 17–29Cite as

Oxidative Damage and Carcinogenesis

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Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 10))

Abstract

Substantial evidence has suggested that free radicals, particularly oxygen radicals, play an important role in several stages of carcinogenesis. Oxidants are ubiquitous in our natural environment but they can also be formed in the tissue by endogenous cellular mechanisms (Cerutti 1985; Kozumbo et al. 1985; Cerutti and Trump 1991). Oxidants can introduce structural damage to DNA, leading to chromosomal aberrations and point mutations. Point mutations in cancer-related genes such as the ras-family protooncogenes (Bos 1989) and the p53 tumor suppressor gene (Hollstein et al. 1991; de Fromentel and Sossi 1992) represent the most frequent genetic changes in human malignancies and at least part of them may be caused by oxidants. Besides these “genotoxic” effects, oxidants activate signal transduction pathways which lead to the modulation of the expression of growth-and differentiation-related genes (Crawford et al. 1988; Shibanuma et al. 1988; Cerutti et al. 1990). However, unlike growth factors oxidants always induce macro-molecular damage, cytotoxicity, and cell killing. The effect of oxidants are influenced by the cellular antioxidant defenses (Cerutti et al. 1988; Amstad and Cerutti 1990) which consist of low-molecular-weight antioxidants and several antioxidant enzymes. The biological consequences of the exposure to an oxidant carcinogen may vary with the dose, the type of oxidant, and the tissue because it is the result of the superposition of effects on multiple cellular targets.

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Authors
  1. P. Amstad
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  2. R. Ghosh
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  3. G. Shah
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  4. Y. Oya
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  5. P. Cerutti
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Andrew Cockburn Lewis Smith

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© 1994 Springer-Verlag Berlin Heidelberg

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Amstad, P., Ghosh, R., Shah, G., Oya, Y., Cerutti, P. (1994). Oxidative Damage and Carcinogenesis. In: Cockburn, A., Smith, L. (eds) Nongenotoxic Carcinogenesis. Ernst Schering Research Foundation Workshop, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-03022-6_2

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  • DOI: https://doi.org/10.1007/978-3-662-03022-6_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-03024-0

  • Online ISBN: 978-3-662-03022-6

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