The quantitative characterization of the dose -response relationship of a panel of yeast (<i>Saccharomyces cerevisiae</i>) strains to prospective antineoplastic agents
This dissertation describes an innovative methodological approach to assess hormetic (biphasic) dose-responses in a single high-throughput study. This approach was applied to data from a National Cancer Institute database that evaluated the capacity of 2,189 candidate antineoplastic drugs to inhibit the growth of 13 yeast strains with and without genetic mutations typical of cancer cells. Evidence of hormesis in these data was assessed in several unique evaluations. Described first, is a method to quantitatively evaluate the concentration-response curves on features pertaining to the magnitude of stimulation, the measure of variation between replications, and the consistency of response across concentrations in the below threshold zone using a novel "Hormetic Metric“. These results are compared to an evaluation of the database using a previously described Hormesis Scoring System. Described next is a quantitative evaluation of the features of the hormetic concentration-responses where the width of the hormetic zone, the width from the maximum stimulation to the toxic threshold (i.e., the zero equivalence point), and the maximum stimulation of the hormetic concentration-responses are all assessed. In a summary evaluation, the evidence of hormesis that was quantified using the previous methodologies is discussed relative to (a) the number of concentrations below the toxic threshold; (b) the chemical compounds toxicity; and (c) the differential response of the various genotypes.