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May ultraviolet light-induced ornithine decarboxylase response in mitotic and postmitotic human skin fibroblasts serve as a marker of aging and differentiation?

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Abstract

Since Hayflick’s pioneering work in the early sixties, human diploid fibroblasts have become a widely accepted in vitro model system for gerontological research. Most recently, Bayreuther and co-workers extended this experimental approach showing that fibroblasts in culture resemble in their design the hemopoietic stem-cell differentiation system. Using this model, we have found in human skin fibroblasts following mitomycin-C (MMC) treatment characteristic morphological changes of the fibroblasts and specific shifts in the [35S]methionine polypeptide pattern of the total cellular proteins which support the notion that MMC accelerates the differentiation pathway from mitotic (MF) to postmitotic fibroblasts (PMF).

Ornithine decarboxylase (ODC) can be activated by ultraviolet light (UV) and is involved in the synthesis of polyamines which play a role in the regulation of DNA synthesis and cell proliferation. Therefore, ODC may participate in the modulation of gene expression. ODC may even serve as a biochemical marker of the mutagenic and carcinogenic effects of ultraviolet light; therefore, we tested this interesting enzyme in the fibroblast differentiation system. Indeed, we were able to show that UV-induced ODC response is significantly reduced in the MMC-induced postmitotic stage of fibroblasts originally derived from a 9-year-old female. We compared this finding with previous results from our laboratory, where we have demonstrated that ODC in human skin fibroblasts from younger donors can be significantly more stimulated by UV compared to the enzyme activities in fibroblasts from older donors. We conclude that UV-induced ODC response may serve as a marker of differentiation and aging. Our results also imply that the fibroblast differentiation system is a very useful tool to unravel the complex mechanisms of skin aging.

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References

  1. Bayreuther, K., Rodemann, H.P., Hommel, R., Dittmann, K., Albiez, M., and P.I. Francz: Human skin fibroblasts in vitro differentiate along a terminal cell lineage. Proc. Natl. Acad. Sci. USA, 85: 5112–5116, 1988.

    PubMed  CAS  Google Scholar 

  2. Rodemann, H.P., Bayreuther, K., Francz, P.I., Dittmann, K., and Albiez, M.: Selective enrichment and biochemical characterization of seven human skin fibroblast cell types in vitro. Expl. Cell Res., 180: 84–93, 1989.

    Article  CAS  Google Scholar 

  3. Bayreuther, K., Francz, P.I., Gogol, J., Hapke, C., Maier, M., and Meinrath, H.-G.: Differentiation of primary and secondary fibroblasts in cell culture systems. Mut. Res., 256: 233–242, 1991.

    CAS  Google Scholar 

  4. Dexter, T.M., Allen, T.D., and Lajtha, L.G.: Conditions controlling the proliferation of haemopoietic stem cells in vitro. J. Cell. Physiol., 91: 335–344, 1977.

    Article  PubMed  CAS  Google Scholar 

  5. Nomura, S., and Oishi, M.: Indirect induction of erythroid differentiation in mouse Friend cells: Evidence for two intracellular reactions involved in the differentiation. Proc. Natl. Acad. Sci. USA, 80: 210–214, 1983.

    PubMed  CAS  Google Scholar 

  6. Marks, P.A., and Rifkind, R.A.: Erythroleukemic differentiation. Ann. Rev. Biochem., 47: 419–448, 1978.

    Article  PubMed  CAS  Google Scholar 

  7. Tuffery, A.A., and Baker, R.S.U.: Alterations of mouse embryo cells during in vitro aging. Expl. Cell Res., 76: 186–190, 1973.

    Article  CAS  Google Scholar 

  8. Hanawalt, P.C., Cooper, P.K., Ganesan, A.K., and Smith, C.A.: DNA repair in bacterial and mammalian cells. Ann. Rev. Biochem., 48: 783–836, 1979.

    Article  PubMed  CAS  Google Scholar 

  9. Brash, D.E., and Haseltine, W.A.: UV-induced mutation hotspots occur at DNA damage hotspots. Nature, 298: 189–192, 1982.

    Article  PubMed  CAS  Google Scholar 

  10. Mitchell, D.L.: The relative cytotoxicity of (6-4) photo-products and cyclobutane dimers in mammalian cells. Photochem. Photobiol., 48: 51–57, 1988.

    Article  PubMed  CAS  Google Scholar 

  11. Niggli, H.J., and Röthlisberger: Sunlight-induced pyrimidine dimers in human skin fibroblasts in comparison with dimerization after artificial UV irradiation. Photochem. Photobiol., 48: 353–356, 1988.

    PubMed  CAS  Google Scholar 

  12. Russell, D.H.: Ornithine decarboxylase as a marker of carcinogenesis — Handbook of carcinogen testing, edited by Milman, H.A. and Weisburger, E.K., Park Ridge, NJ, Noyes Pub., 1985, pp. 464–481.

    Google Scholar 

  13. Connor, M.J., Lowe, N.J., Breeding, J.H., and Chalet, M.: Inhibition of ultraviolet-B skin carcinogenesis by all-trans-retinoic acid regimens that inhibit ornithine decarboxylase induction. Cancer Res., 43: 171–174, 1983.

    PubMed  CAS  Google Scholar 

  14. Protic-Sabljic, M., Tuteja, N., Munson, P.J., Hauser, J., Kraemer, K.H., and Dixon, K.: UV light-induced cyclobutane pyrimidine dimers are mutagenic in mammalian cells. Mol. Cell. Biol., 6: 3349–3356, 1986.

    PubMed  CAS  Google Scholar 

  15. Suzuki, F., Han, A., Lankas, G.R., Utsumi, H., and Elkind, M.M.: Spectral dependencies of killing, mutation and transformation in mammalian cells and their relevance to hazards caused by solar ultraviolet radiation. Cancer Res., 41: 4916–4913, 1984.

    Google Scholar 

  16. Gange, R.W., and Mendelson, R.: Sunscreens block the induction of epidermal ornithine decarboxylase by ultraviolet-B radiation. Br. J. Dermatol., 107: 215–220, 1982.

    PubMed  CAS  Google Scholar 

  17. Arase, S., and Jung, E.G.: In vitro evaluation of the photoprotective efficacy of sunscreens against DNA damage by UVB. Photodermatology, 3: 56–59, 1986.

    PubMed  CAS  Google Scholar 

  18. Blacker, K.L., Williams, M.L., and Goldyne, M.: Mitomycin C-treated 3T3 fibroblasts used as feeder layers for human keratinocytes retain the capacity to generate eicosanoids. J. Invest. Dermatol., 89: 536–539, 1987.

    Article  PubMed  CAS  Google Scholar 

  19. Pritsos, C.A., and Sartorelli, A.C.: Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics. Cancer Res., 46: 3528–3532, 1986.

    PubMed  CAS  Google Scholar 

  20. Cerutti, P.A.: Prooxidant states and tumor promotion. Science, 227: 375–381, 1985.

    PubMed  CAS  Google Scholar 

  21. Friedman, J., Cerutti, P.A.: The induction of ornithine decarboxylase by phorbol 12-myristate 13-acetate or by serum is inhibited by antioxidants. Carcinogenesis, 4:1425–1427, 1983.

    PubMed  CAS  Google Scholar 

  22. Niggli, H.J., and Röthlisberger, R.: Cyclobutane-type pyrimidine photodimer formation and induction of ornithine decarboxylase in human skin fibroblasts after UV irradiation. J. Invest. Dermatol., 91: 5279584, 1988.

    Google Scholar 

  23. Niggli, H.J., and Cerutti, P.A.: Cyclobutane-type pyrimidine photodimer formation and excision in human skin fibroblasts after irradiation with 313 nm ultraviolet light. Biochem., 22: 1390–1395, 1983.

    Article  CAS  Google Scholar 

  24. Niggli, H.J.: Kinetics of excision repair in human skin. J. Invest. Dermatol., 92: 304, 1989.

    Article  PubMed  CAS  Google Scholar 

  25. Niggli, H.J., Bayreuther, K., Rodemann, H.P., Röthlisberger, R., and Francz, P.I.: Mitomycin C-induced postmitotic fibroblasts retain the capacity to repair pyrimidine photodimers formed after UV-irradiation. Mut. Res., 219: 231–240, 1989.

    CAS  Google Scholar 

  26. Seshadri, T., and Campisi, J.: Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. Science, 247: 205–209, 1990.

    PubMed  CAS  Google Scholar 

  27. Chen, K.J., Chang, Z.F., and Liu, A.Y.: Changes of serum-induced ornithine decarboxylase activity and putrescine content during aging of IMR-90 human diploid fibroblasts. J. Cell Physiol., 129: 142–146, 1986.

    Article  PubMed  CAS  Google Scholar 

  28. Gilchrest, B.A.: Skin and aging processes. Boca Raton, CRC Press, 1984.

    Google Scholar 

  29. Macieira-Coelho, A.: Biology of normal proliferating cells in vitro: Relevance for in vivo aging. Interdisciplinary Topics in Gerontology, Vol. 23, Karger, Basel, 1988.

    Google Scholar 

  30. Sano, H., Shiomi, N., Imanishi, K., Maie, O., and Shiomi, T.; DNA methylation in xeroderma pigmentosum. Mut. Res., 217: 141–151, 1989.

    CAS  Google Scholar 

  31. Hayflick, L., and Moorhead, P.S.: The serial cultivation of human diploid cell strains. Expl. Cell Res., 25: 585–621, 1961.

    Article  Google Scholar 

  32. Hayflick, L.: The limited in vitro lifetime of human diploid cell strains. Expl. Cell Res., 37: 614–636, 1965.

    Article  CAS  Google Scholar 

  33. Martin, G.M., Sprague, C.A., and Epstein, C.J.: Replicative life-span of cultivated human cells. Effects of donor’s age, tissue and genotype. Lab. Invest., 23: 86–92, 1970.

    CAS  Google Scholar 

  34. Smith, J.R., Pereira-Smith, O.M., and Schneider, E.L.: Colony size distributions as a measure of in vivo and in vitro aging. Proc. Natl. Acad. Sci. USA, 75: 1353–1356, 1978.

    PubMed  CAS  Google Scholar 

  35. Goldstein, S.: Lifespan of cultured cells in progeria. Lancet, 1: 424, 1969.

    Article  PubMed  CAS  Google Scholar 

  36. Goldstein, S., Moerman, E.J., Soeldner, J.S., Gleason, R.E., and Barnett, D.M.: Chronologic and physiologic age affect replicative lifespan of fibroblasts from diabetic, prediabetic and normal donors. Science, 199: 781–783, 1978.

    PubMed  CAS  Google Scholar 

  37. Gilchrest, B.A.: A quantitative approach to measuring actinic aging in human skin. J. Soc. Cosm. Chem., 32: 153–162, 1981.

    Google Scholar 

  38. Cristofalo, V.J.: Animal cell cultures as a model system for the study of aging, in Advances in Gerontology Research, edited by Strehler New York, Academic Press, 1972, Vol. 4, pp. 45–79.

    Google Scholar 

  39. Martin, G.M., Sprague, C.A., Norwood, T.H., and Pendergrass, W.R.: Clonal selection, attenuation and differentiation as an in vitro model of hyperplasia. Am. J. Path., 74: 137–154, 1974.

    PubMed  CAS  Google Scholar 

  40. Roseeuw, D.I., Marcelo, C.L., and Voorhees, J.J.: Magnitude of ornithine decarboxylase induction by epidermal mitogens: Effect of the assay technique. Arch. Dermatol. Res., 276: 139–146, 1984.

    Article  PubMed  CAS  Google Scholar 

  41. Fleckman, P., Langdon, R., and McGuire, J.: Epidermal growth factor stimulates ornithine decarboxylase activity in cultured mammalian keratinocytes. J. Invest. Dermatol., 82: 85–89, 1984.

    Article  PubMed  CAS  Google Scholar 

  42. Morris, D.R., and Pardee, A.B.: A biosynthetic ornithine decarboxylase in Eschericia coli. Biochem. Biophys. Research Commun., 20: 697–704, 1965.

    Article  CAS  Google Scholar 

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This manuscript was presented during October 1990 at the 20th annual meeting of the American Aging Association and the 16th IFSCC Congress in New York.

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Niggli, H.J., Ftancz, P.I. May ultraviolet light-induced ornithine decarboxylase response in mitotic and postmitotic human skin fibroblasts serve as a marker of aging and differentiation?. AGE 15, 55–60 (1992). https://doi.org/10.1007/BF02435025

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