Abstract
A number of inherited, cancer-prone diseases are associated with severe defects in the abilities of cells to repair damaged DNA (Setlow, 1978; Friedberg, 1985; Maher, this volume; Paterson, this volume). The diseases with the largest defects in repair are xeroderma pigmentosum (XP) and ataxia telangiectasia (AT), the former showing high levels of skin cancer as a result of sunlight irradiation and the latter, high levels of lymphoreticular cancer whose etiologic origins are unknown. The cytotoxic effects of ultraviolet radiation (UV) are much greater on XP cells than on normal cells, whereas the cytotoxic effects of X-rays are much greater on AT cells than on normal ones. It is known that XP cells are defective in one or more DNA repair pathways, but the molecular nature of the defect(s) in AT cells is not known. In XP, the skin cancer susceptibility to sunlight and the cytotoxic effects of UV on their cells in vitro show good correlations with the ability to repair UV-damaged DNA by the process of nucleotide excision. The repair defects range from approximately 20 to 95 percent. It is important to recognize that the repair defects are not 100 percent and actually average somewhere in the neighborhood of 80 percent. This 80 percent average repair defect is associated with an approximately 104-fold increase in skin cancer prevalence (Setlow, 1980; Kraemer et al., 1984) and an approximately 12-fold increase in internal cancers at sites not exposed to sunlight (Kraemer et al., 1984).
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
D’Ambrosio, S.M., Whetstone, J.W., Slazinski, L., and Lowney, E., 1981, Photorepair of pyrimidine dimers in human skin in vivo, Photochem. Photobiol., 34: 461.
Friedberg, E.C., 1985, “DNA Repair,” W.H. Freeman, New York.
Grafström, R.C., Pegg, A.E., Trump, B.F., and Harris, C.C., 1984, O-alkylguanine-DNA alkyltransferase activity in normal human tissues and cells, Cancer Res., 44: 2855.
Kraemer, K.H., Lee, M.Y., and Scotto, J., 1984, DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum, Carcinogenesis, 5: 511.
Lindahl, T., 1982, DNA repair enzymes, Annu. Rev. Biochem., 51: 61.
Myrnes, B., Giercksky, K.E., and Krokan, H., 1983, Interindividual variation in the activity of 0-methylguanine-DNA methyl-transferase and uracil-DNA glycosylase in human organs, Carcinogenesis, 4: 1565.
Nette, E.G., Xi, Y.-P., Sun, Y.-K., Andrews, A.D. and King, D.W., 1984, A correlation between aging and DNA repair in human epidermal cells, Mech. Ageing Dev., 24: 283.
Pegg, A.E., 1984, Repair of -methylguanine in DNA by mammalian tissues, In: “Biochemical Basis of Chemical Carcinogenesis,” pp. 265-274, H. Greim, R. Jung, M. Kramer, M. Marquardt, and F. Oesch, eds., Raven Press, New York.
Scotto, J., Fears, T.R., and Fraumeni, J.F., Jr., 1983, “Incidence of Nonmelanoma Skin Cancer in the United States,” DHHS Pub. No. (NIH) 76 - 1029, Bethesda, MD.
Setlow, R.B., 1978, Repair deficient human disorders and cancer, Nature (London), 271: 713.
Setlow, R.B., 1980, Different basic mechanisms in DNA repair, Arch. Toxicol. Suppl. 3: 217.
Setlow, R.B., 1983, Variations in DNA repair among humans, in: “Human Carcinogenesis,” pp. 231-254, C.C. Harris and H.N. Autrup, eds., Academic Press, New York.
Setlow, R.B., 1985, Saturation of Repair, in: “Assessment of Risks from Low-Level Exposure to Radiation and Chemicals,” in press, A.D. Woodhead, C.J. Shellabarger and V. Pond, Plenum Press, New York.
Sutherland, B.M, Kochevar, I., and Harber, L., 1980, Pyrimidine dimer formation and repair in human skin, Cancer Res., 40: 3181.
Sutherland, B.M., and Oliver, R., 1976, Culture conditions affect photoreactivating enzyme levels in human fibroblasts, Bio- chim. Biophys. Acta, 442: 358.
Waldstein, E.A., Cao, E.-H., Miller, M.E;, Cronkite, E.P., and Setlow, R.B., 1982, Extracts of chronic lymphocytic leukemia lymphocytes have a high level of DNA repair activity for 0-methylguanine, Proc. Natl. Acad. Sci. USA, 79: 4786.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Plenum Press, New York
About this chapter
Cite this chapter
Setlow, R.B. (1985). Variations in DNA Repair Among People. In: Castellani, A. (eds) Epidemiology and Quantitation of Environmental Risk in Humans from Radiation and Other Agents. NATO ASI Series, vol 96. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9445-1_13
Download citation
DOI: https://doi.org/10.1007/978-1-4615-9445-1_13
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4615-9447-5
Online ISBN: 978-1-4615-9445-1
eBook Packages: Springer Book Archive