Trichothecene synergism, additivity, and antagonism: the significance of the maximally quiescent ratio.
The interactive effect of the combinations of trichothecene mycotoxins often found in fungus infected plants, contaminated grain, and other biological systems is poorly understood. Growth inhibition of the yeast Kluyveromyces marxianus was used to measure the effects of HT-2 toxin, roridin A, and T-2 toxin as individual toxins or as binary mixtures. A value, the combination index, was derived which indicates the interactive effects of a binary mixture of toxins. The interaction is affected by the ratio of the individual toxins, and the percent inhibition of yeast growth. Generally the interaction of T-2 toxin and roridin A or T-2 toxin and HT-2 toxin changes from antagonistic when they cause a low percent inhibition of yeast growth to synergistic when they cause a high percent inhibition of yeast growth. Additionally, any two trichothecenes have a unique ratio, which we name the maximally quiescent ratio (or MQR), where there is the least change in the type and intensity of their interaction. The maximally quiescent ratio in this case has helped to define the nature of toxin interactions and could be used to provide insights into hormone, immune system, developmental, enzyme, and gene regulation, combined drug therapy, and the action of mixtures of natural or synthetic toxins, carcinogens, pesticides, and environmental pollutants.
Department of Applied Microbiology and Food Science, University of Saskatchewan, Saskatoon, Canada.
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Koshinsky
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Khachatourians
D004347:Drug Interactions; D004357:Drug Synergism; D007716:Kluyveromyces; D013605:T-2 Toxin / Q000031:analogs & derivatives / Q000633:toxicity; D014255:Trichothecenes / Q000633:toxicity*
D014255:Trichothecenes; D013605:T-2 Toxin; C012351:HT-2 toxin