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Mutagenesis Studies with Cultured Mammalian Cells: Problems and Prospects

  • Chapter
Mutation, Cancer, and Malformation

Part of the book series: Environmental Science Research ((ESRH,volume 31))

Summary

Environmental mutagenesis is thought to play an important role in hereditary and somatic diseases in man. Numerous studies have been made in recent years assaying the mutagenic response of cultured mammalian cells, with the hope of better understanding the effects of environmental agents on human populations. Different test systems have been developed to detect either gene or chromosome mutations at the cellular and molecular levels. Although some of the heritable variations could be epigenetic, direct evidence is available demonstrating that true point mutations indeed occur in mammalian cells. It is now possible to identify specific molecular alterations in mammalian cell mutants arising in vitro.

The development of methods for quantifying single gene mutations in cultured mammalian cells has been considered in this presentation, with special reference to (a) the choice of cell material, (b) development of selective markers, (c) the various factors that affect the expression of mutations, and (d) the application of appropriate statistical methods for the estimation of mutation rates. The role of DNA replication and repair in the mutational process can be illustrated by a concomitant change in mutability, mutagen-sensitivity and other metabolic and genetic alterations in mutant cells that are defective in DNA metabolism.

Recent technical advances have permitted analysis of somatic cell mutants at the protein and nucleic acid levels. Amino acid sequence analysis of certain enzymes and studies on DNA structure changes in cell mutants arising in vitro are now feasible. Furthermore, methods have been developed to screen for various classes of electrophoretic mutants occurring at more than 40 well defined gene loci among cell clones isolated after chemical or physical mutagenesis. Unlike the selective procedures which detect single-locus mutations leading to the loss of a vital function, this multilocus approach has permitted determinations of the frequencies of mutations which result in variant proteins les drastically modified from the wild type. Finally, human somatic cell mutation rates, both spontaneous and induced, at various loci may be estimated by changes in protein products visualized by two-dimensional polyacrylamide gel electrophoresis. The results obtained may afford us the opportunity to compare the mutation rates of functionally vital and selectively neutral markers, as well as those in human somatic and germ cells using the same panel of protein markers.

Supported by research grants GM 20608 and CA 26803 from National Institutes of Health, United States Public Health Service.

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Authors and Affiliations

  1. Department of Human Genetics, University of Michigan Medical School Ann Arbor, Ann Arbor, Michigan, 48109-0010, USA

    Ernest H. Y. Chu, I-Chian Li & Jiliang Fu

  2. School of Public Health, Sichuan Medical College, Chengdu, Sichuan, China

    Jiliang Fu

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  1. Ernest H. Y. Chu
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  1. University of Michigan Medical School, Ann Harbor, Michigan, USA

    Ernest H. Y. Chu

  2. Oak Ridge National Laboratory, Oak Ridge, Tennesse, USA

    Walderico M. Generoso

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Chu, E.H.Y., Li, IC., Fu, J. (1984). Mutagenesis Studies with Cultured Mammalian Cells: Problems and Prospects. In: Chu, E.H.Y., Generoso, W.M. (eds) Mutation, Cancer, and Malformation. Environmental Science Research, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2399-0_16

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