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Age and Species Specific Variation in DNA Excision Repair in Cultured Skin Fibroblasts

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Radiation Carcinogenesis and DNA Alterations

Part of the book series: NATO ASI Series ((NSSA,volume 124))

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Abstract

The suggestion that “DNA repair ” may be a determinant of life span frequently appears in the literature on fundamental aging research (1). This idea is mainly based on the correlation found by Hart and Setlow between the life span of a species and the activity of the excision repair pathway in its UV-irradiated fibroblasts (2). In this vision, rodent cells as compared with human cells would age more rapidly in vivo (maximum life spans of about 4 and 110 years, respectively) and in vitro (about 20 and 60 population doublings, respectively) because of their relatively deficient DNA repair. Following this line of reasoning, it can be hypothesized that the low level of DNA excision repair in rodent cells in comparison with human cells is causally related to the relative instability of the former cell type with respect to immortalization and neoplastic transformation in vitro. In this context it is of interest that (genetically unstable) transformed or tumor-derived mammalian cells are less capable of repairing DNA damage than are their normal counterparts (3, 4, 5). These findings led to the speculation that repair deficiencies may promote genetic alterations characteristic for transformed cells. Viewed in this way, the process of cellular senescence itself may be associated with changes in DNA repair activities leading to neoplastic transformation. This hypothesis is supported by the fact that certain types of cancer, the incidence of which increases greatly with age, have been shown to be associated with deficiencies in certain DNA repair pathways (6, 7). Moreover, decreases in the activities of DNA repair pathways during in vitro and in vivo aging have been frequently reported (8). In this paper we discuss the relevance of one form of DNA repair, excision repair, to the aging process on the basis of the state of the excision repair pathway in rat fibroblasts during in vitro and in vivo aging and the differences in the excision process between normal human and rat fibroblasts.

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Authors and Affiliations

  1. TNO Institute for Experimental Gerontology, P.O. Box 5815, 2280 HV, Rijswijk, The Netherlands

    J. Vijg, E. Mullaart & D. L. Knook

  2. TNO Medical Biological Laboratory, P.O. Box 45, 2280 AA, Rijswijk, The Netherlands

    P. H. M. Lohman

Authors
  1. J. Vijg
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  2. E. Mullaart
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  3. P. H. M. Lohman
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  4. D. L. Knook
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Editors and Affiliations

  1. New York University Medical Center, New York, New York, USA

    F. J. Burns  & A. C. Upton  & 

  2. U.N. Scientific Committee on the Effects of Atomic Radiation, Vienna, Austria

    G. Silini

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© 1986 Springer Science+Business Media New York

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Vijg, J., Mullaart, E., Lohman, P.H.M., Knook, D.L. (1986). Age and Species Specific Variation in DNA Excision Repair in Cultured Skin Fibroblasts. In: Burns, F.J., Upton, A.C., Silini, G. (eds) Radiation Carcinogenesis and DNA Alterations. NATO ASI Series, vol 124. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5269-3_44

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  • DOI: https://doi.org/10.1007/978-1-4684-5269-3_44

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5271-6

  • Online ISBN: 978-1-4684-5269-3

  • eBook Packages: Springer Book Archive

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