Mutation frequencies

Recently, 202 and 203 were found to significantly reduce the mutation frequency induced by BaP in vivo as well (00UP3). Previously, flie same group had pointed out that some genotoxic effects could result from UV irradiation of tryptophan, but this had not been attributed to lipophilic substances like 202 and 203 (94MI5). 

Daugherty, P.S., Chen, G., Iverson, B.L. and Georgiou, G. (2000) Quantitative analysis of the effect of the mutation frequency on the affinity maturation of single chainFv antibodies. Proceedings of the National Academy of Sciences of the United States of America, 97, 2029-2034. 

The observations that mutation frequencies are elevated severalfold above normal levels in mutants which constitutively express their SOS-functions (32) and that the mutation frequency of unirradiated phage is elevated by growing them on irradiated (i.e. SOS-induced) bacteria (33), have been invoked to argue for the notion that mutagenesis via SOS-processing may be indirect. 

Recently, Sage and Haseltine (49) have quantitatively determined the spectrum of DNA lesions induced by reactions of BPDE with DNA. They found that alkali-labile lesions account for about 40% of the DNA adducts. There was a striking correlation between the mutation frequencies induced by BPDE in lacl and the frequencies of alkali sensitive lesions at G, A, and C residues. Apurinic/apyrimidinic sites are common alkali-sensitive lesions. Earlier work by Drink-water e al. (48) had also shown that treatment of DNA with BPDE generated apurinic/apyrimidinic sites. 

The selection of rifaximin-resistant strains was also investigated on five different isolates of H. pylori. None of the strains exhibited primary resistance to rifaximin, but, after exposure to subinhibitory concentrations of the antibiotic, all five strains became resistant. The mutation frequency was similar to that observed with macrolides and quinolones, but was less frequent than that observed with metronidazole [52, 53],... 

Cs mutation frequency was 1.5 daily dose rate of 0.0088 mGy ... 

Heavy metals possess mutagenic effect. The assessment of mutagenic effect was assessed through evaluation of genes recessive mutation frequency in the micronucleus in oral mucous cells of children living at the tested areas (Tabl. 3). 

There was no increase in mutation frequency at the hypoxanthine-guanine phosphoribosyl transferase gene locus in the presence or absence of S9 (Bootman et al. 1988b), and results were negative in a DNA repair assay with E. coli (Hodson-Walker and May 1988). 

The trypsinized cultures are counted and a sample is assessed for survival as for the cytotoxicity assay. In addition, an appropriate number of cells are reseeded for estimation of mutation frequency at the day 8 expression time. The cells are transferred to roller bottles (usually 490 cm2) for this stage. The bottles are gassed with pure CO2, the tops are tightened and the bottles are incubated at 37°C on a roller machine (approximate speed 0.5-1.0 rev min-1). Usually 106 7 8 9 viable cells are reseeded in 50 ml of Eagle s medium containing serum, but more cells are required at the toxic dose levels. 

Data Analysis. (Arlett et al., 1989). A weighted analysis of variance is performed on the mutation frequencies, as the variation in the number of mutations per plate usually increases as the mean increases. Each dose of test compound is compared with the corresponding vehicle control by means of a one-sided Dunnett s test and, in addition, the mutation frequencies are examined to see whether there is a linear relationship with dose. 

The criterion employed for a positive response in this assay is a reproducible statistically significant increase in mutation frequency (weighted mean for duplicate treated cultures) over the concurrent vehicle control value (weighted mean for four independent control cultures). Ideally, the response should show evidence of a dose-response relationship. When a small isolated significant increase in mutation frequency is observed in only one of the two duplicate experiments, then a third test should be carried out. If the third test shows no significant effects, the initial increase is likely to be a chance result. In cases where an apparent treatment-related increase is thought to be a result of unusually low variability or a low control frequency, comparison with the laboratory historical control frequency may be justified. 

Each culture is counted so that a sample of cells can be assessed for posttreatment survival, and the remaining cell population assessed for estimation of mutation frequency. 

Comparison of mutation frequencies is made with the historical database. For definition of a positive result the same principles are recommended as for the mouse spot test (Selby and Olson, 1981). A minimum size of 18,000 offspring per group is recommended by those authors for definition of a negative result. 

Cell name Mutagens Selective agents Mutating frequency Phenotype sign Reverse frequency... 

Mitotic abnormalities Back mutation frequency Chromosomal aberrations... 

Most studies indicate that malathion is not genotoxic, although some tests indicate that it can produce chromosomal aberrations and sister chromatid exchanges in vitro There was no significant increase in mutation frequency or micronucleus formation in a cohort of California workers involved in application of malathion as ground treatment during the 1990s. ... 

In general exposure to zinc chloride does not increase mutation frequencies in bacterial or mammalian test systems. ... 

Mutagenesis Oxcarbazepine increased mutation frequencies in the Ames test in vitro in the absence of metabolic activation in 1 of 5 bacterial strains. Oxcarbazepine and MHD produced increases in chromosomal aberrations and polyploidy in the Chinese hamster ovary assay in vitro in the absence of metabolic activation. 

The bacterial and mammalian cell assays for gene mutation were developed to measure statistically significant increases in the numbers of mutant colonies derived from rare events many millions of exposed cells must be plated out to allow the assessment of mutation frequency. The Salmonella typhimurium reverse mutation assay ( Ames test) is carried out in a variety of different mutant strains selected to identify the various classes of mutation. The test generates many hundreds of Petri dishes for counting and is not practical for profiling. 

Zebrafish Brachydanio/Danio rerio) embryos can be produced in large numbers and carry sufficient nutrients within the egg sack to allow development within micro plate volumes [52, 53]. Mutation frequency has been estimated indirectly using transgenic fish [54[ and UDS, comet, MNT and alkaline filter elution methods have been used effectively [55]. At present, there has been insufficient study of the model to understand predictivity of mammalian genotoxicity, and none of the methods has been demonstrated at throughputs sufficient for hit and lead screening. 

Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania neonatal screening shows high incidence and unexpected mutation frequencies. 

In order to compare mutation frequency induced by 220-MeV C ions with that by low-LET radiation (electrons), Arabidopsis visible phenotype loci were chosen as follows transparent testa tt) whose seed coat is transparent because of lack of pigment glaborous gl), which have no hair on their leaves and stems and long hypocotyl hy) whose hypocotyl is longer than that of the wild type in the light condition. Mutation frequencies of tt, gl, and hy induced by carbon ions were 8- to 34-fold higher than those by electrons (Table 2). In this study, irradiation doses for the induction of mutation were determined from the RBE of carbon ions compared with that of electrons on the survival of plants, which was approximately 5. Both doses are at three-quarters of the shoulder dose of each survival curve [104]. 

Table 2 Mutation Frequency Induced by Carbon Ions and Electrons...

Mutagen (dose) Locus Mutation frequency/locus/diploid cell/dose (Gy) (x 10 )... 

Other Plants. As already described in Mutation Spectrum, complex and striped types of flower color have been obtained in chrysanthemum. A higher mutation frequency... 

Like many other Irritants, PS has not been tested thoroughly for mutagenicity. However, in one early study, Auerbach tested its capacity to Induce sex-linked recessive lethal mutations In the fruit fly, Drosophila melanogaster. In all broods of flies derived from PS-treated males, the mutation frequencies were consistent with those of untreated laboratory stocks. A total of 4,454 chromosomes were tested, and the mutation frequency was 0.2%. In contrast, flies treated with mustard gas had a frequency of 5.2%. 

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