MAST suit 'myths' are dispelled as effects become understood.
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Biomedical subjects
Publications and source records attributed to J McCann.
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Both the spontaneous and the induced mutation rates in Salmonella tester strains vary among different laboratories, and also within the same laboratory over time. If there is an association between spontaneous and induced mutagenesis, a measure of mutagenic potency that incorporates the background may be more consistent than the simple measure of the induced slope. We have used the statistical procedures recently described by Bernstein et al. (1982), and a large data-base of Salmonella test results to examine the association between spontaneous and induced mutation and to compare several alternative measures of mutagenic potency. A correlation analysis indicated an association between spontaneous and induced mutation for TA98, TA1537 and TA1535; TA1538 was close to being significant. This was observed over a wide range of chemicals. In addition, for TA98, for which we observed the strongest association, we obtained a rough estimate of the relationship between slope and intercept by using least squares to fit K and p in the power curve beta = k alpha p. We then chose 3 simple potency measures: the slope, the ratio of slope to spontaneous background, and the ratio of slope to the square-root of spontaneous background. These corresponded to the range of p's estimated from the least-squares fit procedure. The reproducibility of these measures was compared and no significant differences were found. Though there were some differences in the relative potency ranking of chemicals using the different measures, they were highly correlated.
Of all the chemicals present in our environment, which cause cancer and which do not? Since whole-animal bioassays are too expensive and time-consuming for routine screening, attention has focused on short-term in vitro and in vivo tests that generally demonstrate mutagenesis or other forms of chemical interaction with DNA. Merits and limitations of these tests are discussed.
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A number of recent papers have suggested basing the statistical analysis of Salmonella (Ames) mutagenicity test results on a mathematical model of the complete dose-response curve. For most mutagens at low doses the curve increases linearly; then, as the dose increases, the curve may flatten and finally turn downwards due primarily to effects of toxicity. The exact mechanism underlying this shape is, however, not well understood and is likely to vary for different chemicals. A different approach is to assume that the initial part of the curve is linear and to base the statistical analysis solely on this region, reasoning that it contains most of the interpretable information about the mutagenesis dose response. In this paper a formal method of deciding which points are on the initial linear part of the curve is described, and a statistical method is proposed for analyzing these points. Computer simulations are used to examine the properties of the procedure and comparisons are made with a previously proposed mathematical model of the whole curve. It is concluded that the method suggested here provides a very satisfactory, robust method for the standard analysis of Salmonella data.
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