Skip to main content
SpringerLink
Log in
Book cover

Short-Term Bioassays in the Analysis of Complex Environmental Mixtures III pp 229–244Cite as

Relationship(S) between Mutation and Cytotoxicity Induced in Vitro

  • Chapter

  • 108 Accesses

Part of the book series: Environmental Science Research ((ESRH,volume 27))

Abstract

Rapid, short-term tests are currently used to identify compounds mutagenic in vitro. In vivo tests are then used to confirm a compound’s activity in the intact animal and to assess oncogenic and genetic risk. Carver et al. (1979) presented the hypothesis that cytotoxicity induced by an agent in vitro might estimate potential mutagenicity in vivo. They compared the induced mutation frequency per unit exposure dose (M) of 22 known mutagens with the unit decrease in survival; a relative increase in cytotoxicity (defined as the failure of cultured cells to undergo continued cell division) was usually accompanied by a proportional increase in mutagenicity. The correlation between cytotoxicity and mutagenicity does not necessarily imply that lethal and mutagenic events arise from the same type of lesion; factors such as (de)toxification, biochemical reactions, and repair mechanisms may affect both end points. The relationship implies, however, that the maximum potential mutagenic potency of agents in vitro might be estimated from measurement of cytotoxic potency. Some compounds highly toxic in vitro are not significantly mutagenic in vitro, but agents rarely induce mutation in the complete absence of a dose-related increase in toxicity.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adair, G.M., J.H. Carver, and D.L. Wandres. 1980. Mutagenicity testing in mammalian cells, I: derivation of a Chinese hamster ovary cell line heterozygous for the adenine phosphoribosyltransferase and thymidine kinase loci. Mutation Res. 72:187–205.

    Article  Google Scholar 

  • Adair, G.M. and J.H. Carver. (MS). Mutagenicity testing in mammalian cells, III: induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells.

    Google Scholar 

  • Amacher, D.E., S.C. Paillet, and J.A. Elliott. 1981. The metabolism of N-acetyl-2-aminofluorene to a mutagen in L5178Y/TK+/- mouse lymphoma cells. Mutation Res. 89:311–320.

    Article  Google Scholar 

  • Baker, R.M., W.C. Van Voorhis, and L.A. Spencer. 1979. HeLa cell variants that differ in sensitivity to monofunctional alkylating agents, with independence of cytotoxic and mutagenic responses. Proc. Natl. Acad. Sci. USA 76:5249–5253.

    Article  ADS  Google Scholar 

  • Bhuyan, B.K., A.R. Peterson, and C. Heidelberger. 1976. Cytotoxicity, mutations and DNA damage produced in Chinese hamster cells treated with streptozotocin, its analogs, and N-methyl-N’-nitro-N-nitrosoguanidine. Chem.-Biol. Interact. 13:173–179.

    Article  Google Scholar 

  • Bradley, M.O. and L.C. Erickson. 1981. Comparison of the effects of hydrogen peroxide and X-ray irradiation on toxicity, mutation, and DNA damage/repair in mammalian cells (V-79). Biochim. Biophys. Acta 654:135–141.

    Google Scholar 

  • Bradley, M.O., N.A. Sharkey, K.W. Kohn, and M.W. Layard. 1980. Mutagenicity and cytotoxicity of various nitrosoureas in V-79 Chinese hamster cells. Cancer Res. 40:2719–2725.

    Google Scholar 

  • Bridges, B.A. 1975. The mutagenicity of captan and related fungicides. Mutation Res. 32:3–34.

    Google Scholar 

  • Carver, J.H., G.M. Adair, and D.L. Wandres. 1980. Mutagenicity testing in mammalian cells, II: validation of multiple drug-resistance markers having practical application for screening potential mutagens. Mutation Res. 72:207–230.

    Article  Google Scholar 

  • Carver, J.H., F.T. Hatch, and E.W. Branscomb. 1979. Estimating maximum limits to mutagenic potency from cytotoxic potency. Nature 279:154–156.

    Article  ADS  Google Scholar 

  • Clive, D., K.D. Johnson, J.F.S. Spector, A.G. Batson, and M.M.M. Brown. 1979. Validation and characterization of the L5178Y/TK+/- mouse lymphoma mutagen assay system. Mutation Res. 59:61–108.

    Article  Google Scholar 

  • Cole, J. and C.F. Arlett. 1976. Ethyl methanesulfonate mutagenesis with L5178Y mouse lymphoma cells: a comparison of ouabain, thioguanine and excess thymidine resistance. Mutation Res. 34:507–526.

    Article  Google Scholar 

  • Cole, J. and C.F. Arlett. 1978. Methyl methanesulfonate mutagenesis in L5178Y mouse lymphoma cells. Mutation Res. 50:111–120.

    Article  Google Scholar 

  • Couch, D.B. and A.W. Hsie. 1978. Mutagenicity and cytotoxicity of congeners of two classes of nitroso compounds in Chinese hamster ovary cells. Mutation Res. 57:209–216.

    Article  Google Scholar 

  • Couch, D.B., N.L. Forbes, and A.W. Hsie. 1978. Comparative mutagenicity of alkylsulfate and alkanesulfonate derivatives in Chinese hamster ovary cells. Mutation Res. 57:217–224.

    Article  Google Scholar 

  • Frantz, C.N. and H.V. Mailing. 1976. Bromodeoxyuridine resistance induced in mouse lymphoma cells by microsomal activation of dimethylnitrosamine. J. Toxicol. Environ. Health 2:179–187.

    Article  Google Scholar 

  • Fuscoe, J.C, J.P. O’Neill, R.M. Peck, and A.W. Hsie. 1979. Mutagenicity and cytotoxicity of nineteen heterocyclic mustards (ICR compounds) in cultured mammalian cells. Cancer Res. 39:4875–4881.

    Google Scholar 

  • Haag, S.M. and I.G. Sipes. 1980. Differential effects of acetone or Aroclor 12 54 pretreatment on the microsomal activation of dimethylnitrosamine to a mutagen. Mutation Res. 74:431–438.

    Google Scholar 

  • Hsie, A.W., P.A. Brimer, T.J. Mitchell, and D.G. Gosslee. 1975. The dose-response relationship for ethyl methanesulfonate-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells. Somatic Cell Genet. 1:247–261.

    Article  Google Scholar 

  • Hsie, A.W., P.A. Brimer, J.P. O’Neill, J.L. Epier, M.R. Guerin, and M.H. Hsie. 1980. Mutagenicity of alkaline constituents of a coal-liquified crude oil in mammalian cells. Mutation Res. 78:79–84.

    Article  Google Scholar 

  • Hsu, I., G.T. Bowden, and C.C. Harris. 1979. A comparison of cytotoxicity, ouabain-resistant mutation, sister-chromatid exchanges, and nascent DNA synthesis in Chinese hamster cells treated with dihydrodiol epoxide derivatives of benzo(a)pyrene. Mutation Res. 63:351–359.

    Article  Google Scholar 

  • Lassiter, D.V. 1977. Occupational Carcinogenesis. In: Advances in Modern Toxicology, Volume 3: Environmental Cancer. H.F. Kraybill and M.A. Mehlman, eds. John Wiley and Sons: New York. pp. 63–86.

    Google Scholar 

  • McCann, J. and B.N. Ames. 1976. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals, discussion. Proc. Natl. Acad. Sci. USA 73:950–954.

    Article  ADS  Google Scholar 

  • Johnson, N.P., J.D. Hoeschele, R.O. Rahn, J.P. O’Neill, and A. W. Hsie. 1980. Mutagenicity, cytotoxicity, and DNA binding of platinum (II)-chloroamines in Chinese hamster ovary cells. Cancer Res. 40:1463–1468.

    Google Scholar 

  • Jones, D.C.L., V.F. Simmon, K.E. Mortelmans, A.D. Mitchell, E.L. Evans, M.M. Jotz, E.S. Riccio, D.E. Robinson, and B. A. Kirkhart. (MS). In vitro mutagenicity studies of environmental chemicals. SRI Project LSU-7558; contract No. 68–02–2947. U.S. Environmental Protection Agency.

    Google Scholar 

  • Kuroki, T., C. Drevon, and R. Montesano. 1977. Microsome-mediated mutagenesis in V79 Chinese hamster cells by various nitrosamines. Cancer Res. 37:1044–1050.

    Google Scholar 

  • Mitchell, A.D., E.L. Evans, E.S. Riccio, K.E. Mortelmans, and V.F. Simmon. 1980. Mutagenic and carcinogenic potency of extracts of diesel and related environmental emissions: In vitro mutagenesis and DNA damage. In: Health Effects of Diesel Engine Emissions. W.E. Pepelko, R.M. Danner, and N.A. Clarke, eds. EPA-600/9–80–057b. U.S. Environmental Protection Agency: Cincinnati, OH. pp. 810–840.

    Google Scholar 

  • Murthy, M.S.S. and K.B. Najaria. 1980. Deactivation of furyl furamide (AF-2) by rat-liver microsomes and its implication in short-term tests for mutagenicity/carcinogenicity. Mutation Res. 77:127–134.

    Article  Google Scholar 

  • O’Neill, J.P., P.A. Brimer, R. Machanoff, G.P. Hirsch, and A.W. Hsie. 1977. A quantitative assay of mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system): development and definition of the system. Mutation Res. 45:91–101.

    Article  Google Scholar 

  • O’Neill, J.P., D.B. Couch, R. Machanoff, J.R. San Sebastian, P.A. Brimer, and A.W. Hsie. 1977. A quantitative assay of mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system): utilization with a variety of mutagenic agents. Mutation Res. 45:103–109.

    Article  Google Scholar 

  • O’Neill, J.P. and A.W. Hsie. 1977. Chemical mutagenesis of mammalian cells can be quantified. Nature 269:815–817.

    Article  ADS  Google Scholar 

  • O’Neill, J.P., J.C. Fuscoe, and A.W. Hsie. 1978. Mutagenicity of heterocyclic nitrogen mustards (ICR compounds) in cultured mammalian cells. Cancer Res. 38:506–509.

    Google Scholar 

  • O’Neill, J.P. and A.W. Hsie. 1979. Phenotypic expression time of mutagen-induced 6-thioguanine resistance in Chinese hamster ovary cells (CHO/HGPRT system). Mutation Res. 59:109–118.

    Article  Google Scholar 

  • O’Neill, J.P., N.L. Forbes, and A.W. Hsie. 1981. Cytotoxicity and mutagenicity of the fungicides captan and folpet in cultured mammalian cells (CHO/HGPRT system). Environ. Mutagen. 3:233–237.

    Article  Google Scholar 

  • Peterson, A.R., H. Peterson, and C. Heidelberger. 1979. Oncogenesis, mutagenesis, DNA damage, and cytotoxicity in cultured mammalian cells treated with alkylating agents. Cancer Res. 39:131–138.

    Google Scholar 

  • Raffetto, G., S. Parodi, P. Faggin, and A. Maconi. 1974. Relationship between cytotoxicity and induction of sister-chromatid exchanges in mouse foetal cells exposed to several doses of carcinogenic and non-carcinogenic chemicals. Mutation Res. 63:335–343.

    Google Scholar 

  • Rogers, A.M. and K.C. Back. 1981. Comparative mutagenicity of hydrazine and 3 methylated derivatives in L5178Y mouse lymphoma cells. Mutation Res. 89:321–328.

    Article  Google Scholar 

  • Suter, W., J. Brennand, S. McMillan, and M. Fox. 1980. Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells: independence of cytotoxic and mutagenic responses. Mutation Res. 73:171–181.

    Article  Google Scholar 

  • Tezuka, H., N. Ando, R. Suzuki, M. Terahata, M. Moriya, and Y. Shirasu. 1980. Sister-chroraatid exchanges and chromosomal aberrations in cultured Chinese hamster cells treated with pesticides positive in microbial reversion assays. Mutation Res. 78:177–191.

    Article  Google Scholar 

  • Van Zeeland, A.A. and J.W.I.M. Simons. 1976. Linear dose-response relationships after prolonged expression times in V79 Chinese hamster cells. Mutation Res. 35:129–138.

    Article  Google Scholar 

  • Waters, M.D., S.S. Sandhu, V.F. Simmon, K.E. Mortelmans, A.D. Mitchell, T.A. Jorgenson, D.C.L. Jones, R. Valencia, and N.E. Garrett. (In Press). Study of pesticide genotoxicity. In: Genetic Toxicology: An Agricultural Perspective. R. Fleck and A. Hollaender, eds. New York: Plenum Press.

    Google Scholar 

  • Wild, D. 1975. Mutagenicity of the food additive AF-2, a nitrofuran, in Escherichia coli and Chinese hamster cells in culture. Mutation Res. 31:197–199.

    Google Scholar 

  • Wood, A.W., R.L. Chang, W. Levin, D.E. Ryan, P.E. Thomas, M. Croisy-Delcey, Y. Ittah, H. Yagi, D.M. Jerina, and A.H. Conney. 1980. Mutagenicity of the dihydrodiols and bay-region diol-epoxides of benzo(c)phenanthrene in bacterial and mammalian cells. Cancer Res. 40:2876–2883.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chevron Environmental Health Center, 94802, Richmond, CA, USA

    J. H. Carver

  2. Biochemical Genetics Department, SRI International, 94025, Menlo Park, CA, USA

    A. D. Mitchell

  3. Genetic Toxicology Division, Health Effects Research Laboratory, U.S. Environmental Protection Agency, 27711, Research Triangle Park, NC, USA

    M. D. Waters

Authors
  1. J. H. Carver
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. D. Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. D. Waters
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. U. S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA

    Michael D. Waters , Shahbeg S. Sandhu , Joellen Lewtas , Larry Claxton , Neil Chernoff  & Stephen Nesnow , , , ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Plenum Press, New York

About this chapter

Cite this chapter

Carver, J.H., Mitchell, A.D., Waters, M.D. (1983). Relationship(S) between Mutation and Cytotoxicity Induced in Vitro . In: Waters, M.D., Sandhu, S.S., Lewtas, J., Claxton, L., Chernoff, N., Nesnow, S. (eds) Short-Term Bioassays in the Analysis of Complex Environmental Mixtures III. Environmental Science Research, vol 27. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3611-2_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-3611-2_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3613-6

  • Online ISBN: 978-1-4613-3611-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation