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Physical-Chemical Methods for the Detection of the Effect of Mutagens on DNA

  • Chapter
Chemical Mutagens

Abstract

Mutation is a hereditible change in the DNA of an organism. All mutagens must therefore alter the structure of DNA either directly or indirectly. However, there are imposing barriers to the study of the mutagenic effectiveness of particular compounds by determination of the physical changes they produce in DNA. The major problem comes from the amplification factor inherent in gene action. The DNA of an organism such as the bacterium Escherichia coli, with a total molecular weight of about 4.7 × 109, will contain about 1.6 × 107 nucleotides (McQuillen, 1965). A change in any one of these nucleotides may produce a recognizable mutation. Yet most standard chemical methods are unable to detect changes of one part per thousand, let alone one per 20,000,000. Furthermore, the mutagenic reaction is not necessarily the only, or even the major, change produced by reaction of DNA with a mutagen. For example, nitrous acid deaminates bases (Schuster, 1960) and should lead to transition mutations, but it also produces crosslinks (Becker et al., 1964) by an unknown mechanism and leads to large deletions of genetic material (Tessman, 1962). In many cases, the putative mutagen may not even be the actual one and the compound may be transformed in vivo into the actual mutagen (Legator et al., 1969; Leahy et al., 1967; Kojima and Ichibagase, 1966). In such cases, in vitro mixture of the original, nontransformed compound and DNA will give no meaningful result.

The work reported from this laboratory was supported by grants from the National Institutes of Health (USPHS 2 R01 GM 07816), the National Science Foundation (NSF GB 8514), and the Atomic Energy Commission (AEC AT (11–1) 2040)).

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Abbreviations

EMS:

ethyl methanesulfonate

MMS:

methyl methanesulfonate

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© 1971 Plenum Press, New York

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Strauss, B.S. (1971). Physical-Chemical Methods for the Detection of the Effect of Mutagens on DNA. In: Hollaender, A. (eds) Chemical Mutagens. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8966-2_5

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