Multi-well Assay for Unscheduled DNA Synthesis Using Human Diploid Fibroblasts

  • George R. Douglas
  • Caroline E. Grant
  • Judith M. Wytsma
  • Anthony Chan
Conference paper
Part of the Topics in Environmental Physiology and Medicine book series (TEPHY)


There is concern that man is being exposed to substances that have the potential to cause genetic disease. The development of a number of short-term tests for mutagenic activity (Kilbey et al., 1977; Montesano et al., 1976) has greatly facilitated the task of identifying mutagenic substances, and since it has been demonstrated that many mutagens are also carcinogens (McCannet al., 1975), these substances may also be carcinogenic. Short-term tests for mutagenic activity can be divided into two groups: (1) tests that result in specific types of mutation events (i.e., point mutation or chromosome aberration) that are directly detected as phenotypic changes; and (2) tests that detect effects that correlate with genetic events. These latter effects may be precursor events which could ultimately, but not necessarily, lead to the formation of mutations. This category includes tests for induction of DNA damage and stimulation of unscheduled DNA synthesis (Stich et al., 1976). Since they do not require the detection of a specific genotypic change which may require a rigid set of conditions, these indicator tests may be considered more universal in their ability to detect genetic activity. Thus they serve as an important adjunct to tests which measure mutations directly.


Test Chemical Ethyl Methane Sulfonate Human Diploid Fibroblast Ethyl Methane Sulfonate Repair Replication 
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  1. Ames, B.N., McCann, J., Yamasaki, E. (1975): Methods for detecting carcinogens and mutagens with Salmonellamammalian-microsome mutagenicity test. Mutat. Res. 31: 347–364.PubMedGoogle Scholar
  2. Andrae, U., Greim, H. (1979): Induction of DNA repair replication by hydroxyurea in human lymphoblastoid cells mediated by liver microsomes and NADPH. Biochem. Biophys. Res. Comm. 87: 50–58.Google Scholar
  3. Brandt, W.N., Flamm, W.G., Bernheim, N.J. (1972): The value of hydroxyurea in assessing repair synthesis of DNA in HeLa cells. Chem. Biol. Interact. 5: 327–339.PubMedCrossRefGoogle Scholar
  4. Clarkson, J.M. (1978): Enhancement of repair replication in mammalian cells by hydroxyurea. Mutat. Res. 52: 273–284.PubMedCrossRefGoogle Scholar
  5. Ho, T.Y., Quinn, P.A. (1977): Rapid detection of Mycoplasma in tissue culture by SEM. Scanning Electron Microscopy/1977, 2: 291–299.Google Scholar
  6. Kilbey, B.J., Legator, M., Nichols, W., Ramel, C. (eds.) (1977): Handbook of Mutagenicity Test Procedures. Amsterdam, Elsevier/North Holland Biomedical Press.Google Scholar
  7. Martin, C.N., McDermid, A.C., Garner, R.C. (1978): Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res. 38: 2621–2621.PubMedGoogle Scholar
  8. McCann, J., Choi, E., Yamasaki, E., Ames, B.N. (1975): Detection of carcinogens as mutagens in the Salmonellalmicrosomal test: Assay of 300 chemicals. Proc. Natl Acad. Sei. USA 72: 5135–5139.CrossRefGoogle Scholar
  9. McMahon, R.E., Cline, J.C., Thompson, C.Z. (1979): Assay of 855 test chemicals in ten tester strains using a new modification of the Ames test for bacterial mutagens. Cancer Res. 39: 682–693.PubMedGoogle Scholar
  10. Montesano, R., Bartsch, H., Tomatis, L. (eds.) (1976): Screening Tests in Chemical Carcinogenesis, I ARC Scientific Publications No. 12, Lyon, International Agency for Research on Cancer. Painter, R.B. (1977): Rapid test to detect agents that damage human DNA. Nature (Lond.), 265:650–651.Google Scholar
  11. Painter, R.B. (1997): Rapid test to detect agents that damage human DNA. Nature (Lond.), 265:650–651Google Scholar
  12. Stich, H.F., San, R.H.C. (1970): DNA repair and chromatid anomalies in mammalian cells exposed to 4-nitroquinoline-l-oxide. Mutat. Res. 10: 389–404.PubMedCrossRefGoogle Scholar
  13. Stich, H.F., Lam, P., Lo, L.W., Koropatnick, D. J., San, R.H.C. (1975): The search for relevant short-term bioassays for chemical carcinogens: the tribulation of a modern Sisyphus. Can. J. Genet. Cytol. 77: 471–492.Google Scholar
  14. Stich, H.F., San, R.H.C., Lam, P., Koropatnick, D.J., Lo, L.W., Laishes, B.A. (1976): DNA fragmentation and DNA repair as an in vitro and in vivo assay for chemical precarcinogens, carcinogens and carcinogenic nitrosation products. In: R. Montesano, H. Bartsch, and L. Tomatis (eds.), Screening Tests in Chemical Carcinogenesis, IARC Scientific Publications No. 12, Lyon, International Agency for Research on Cancer, pp. 617–636.Google Scholar
  15. Williams, G. (1977): Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Res. 37: 1845–1851.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1981

Authors and Affiliations

  • George R. Douglas
  • Caroline E. Grant
  • Judith M. Wytsma
  • Anthony Chan

There are no affiliations available

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