Mutagen specificity

Essigmann, J.M. and Wood, M.L. (1993). The relationship between the chemical structures and mutagenic specificities of the DNA lesions formed by chemical and physical mutagens. Toxicol. Lett. 67, 29-39. 

We have applied the genetic system for analyzing lacl nonsense mutants to the investigation of the mutagenic specificity of benzo-... 

Work in my laboratory has been supported by grants from the NIH. I am indebted to many of my present and former colleagues, in particular to Drs. A.J. Warren and P.L. Foster for their work on the mutagenic specificity of chemical carcinogens and to Dr. J.H. Miller for his collaborative effort in studying the mutagenic specificity of benzola]pyrene and aflatoxin B. ... 

Rodriguez H, Loechler EL. 1993. Mutational specificity of the (+) - anti-diol epoxide of benzo [a] pyrine in a supF gene of an Escherichia coli plasmid DNA sequence context influences hotspots, mutagenic specificity and the extent of SOS enhancements of mutagenesis. Carcinogenesis 14(3) 373-383. 

Zimmermann, F.K. Vig, B.K. (1975) Mutagen specificity in the induction of mitotic crossing-over in Saccharomyces cerevisiae. Mol. gen. Genet., 139, 255-268... 

Premaratne, S., Mandel, M. Mower, H.F. (1995) Detection of mutagen specific adduct formation in DNA using sequencing methodology. Int. J. Biochem. Cell Biol., 27, 789-794 Quintero-Ruiz, A., Paz-Neri, L.L. Villa-Trevino, S. (1981) Indirect alkylation of CBA mouse... 

Shukla, PT. (1972) Analysis of mutagen specificity in Drosophila melanogaster. Mutat. Res., 16, 363-371... 

About 7,000 F2 cultures are required to determine whether the spontaneous rate was at least doubled by the treatment. Obviously, fewer tests cure needed for mutagens that induce very large mutation rates. If a significant increase in recessive-lethal frequency has not been observed in 7,000 tests of the treated group, the treatment is considered to be negative. Finally, it should be stressed that, with 800 different test genes distributed over the X chromosome, unique DNA-mutagen specificities should be detectable. 

Mutagen specificity meant something different to plant breeders than it did to geneticists working on the mechanisms of mutation. For plant breeders, the central problem was phenotypic specificity, where the outcome was a phenotypic characteristic such as disease resistance or straw stiffness (in the case of barley). Here, the ends outweighed the means in economic importance. More fundamental locus specificity and the origins of mutational outcomes were less important to breeders (Auerbach 1976 453-454). 

The basis for Auerbach s concern was rooted in the double-edged facts of mutagen specificity. Experiments dating from the 1940s demonstrated that mutation is not one thing, or even one class of things, but instead a complex of... 

Shibutani, S., Suzuki, N., and Grollman, A.P. (1998) Mutagenic specificity of (acetylamino)-fluorene-derived DNA adducts in mammalian cells. Biochemistry, 37,12034-12041. 

Reid TM, Loeb LA (1992) Mutagenic specificity of oxygen radicals produced by human leukemia cells. Cancer Res 52 1082-1086... 

There is little evidence for mutagenicity of iron compounds in mammalian cells, although there is in bacteria (Table 1). Like copper, iron is also a well-known Fenton reagent participant. In both cases, mammalian cells are protected from potential Fenton reactions by these essential metals by sequestering them. Like Cu(II), Fe(III) also acts as a photosensitizer with UV (Larson et al. 1992). Fe(II) was reported to enhance SA7 virus transformation (Casto et al. 1979). Treatment of plasmid DNA with Fe(II) caused G C transversions most frequently, followed by C T transitions and G T transversions McBride et al. 1991). It is of interest that the mutagenic specificity of Fe(II) was different from that of Cu(II) (see above). 

B. N. Ames and K. Hooper, Does carcinogenic potency correlate with mutagenic specificity in the Ames assay A reply. Nature (London) 274, 19-20 (1978). 

In 1948, Fries and Kihlman in Sweden reported the production of auxotrophic mutations in the ascomycete Ophiostoma multiannulatum by prolonged immersion of the conidia in solutions of caffeine (0.2%) or theophylline (0.6%). Either treatment yielded about 1% auxotrophs at survival levels of about 0.2% control mutation frequencies were very low. Qualitatively, the results were especially interesting because they showed a difference between the mutational spectra induced by these two purines on the one hand and X-irradiation on the other. This was most striking for inositol requirers, which formed less than 5% of radiation-induced auxotrophs but more than 40% of purine-induced ones. This is one of the rare cases of mutagen specificity for a whole locus or biochemical pathway. Like similar cases that were subsequently reported from the same laboratory, it may rest on selective effects of the plating medium, amplified by the previous treatment of the plated conidia. 

The problem of mutagen specificity as far as plating-medium effects are concerned has to be borne in mind for a proper evaluation of the data obtained. Actually, it is the complications introduced by these phenomena which make a simple cookbook type of approach to routine screening for mutagenicity impossible. 

---