This project continues a detailed investigation of an hepatotoxic metabolite, rubratoxin B, elaborated by a food-storage fungus, Penicillium rubrum. Its molecular toxicity will be ascertained in susceptible animals and its pathological effects noted to determine the molecular mechanism(s) of action. Biochemical investigations will be undertaken to determine metabolic alterations, i.e., changes in enzyme activity. Effects, of isolated tissue, cell and particulate fractions (mitochondria, lysosomes, microsomes) will be examined. Such knowledge of effects of rubratoxin B on an enzyme(s) or transport system would assist greatly in constructing a picture of the events when whole animals are poisoned by the compound. The reactivity of rubratoxin in an animal organism will be studied by examining its metabolic products. Such studies will employ toxicological methods and radiolabeled rubratoxin. After identification of the metabolic products, the enzymic mechanisms by which these metabolites are produced will be examined. With this knowledge the causal chain of events leading to death or illness can be examined. The metabolic reactions which modify the toxicity of the mycotoxin and its effect on the mechanism of toxicity can then be considered. It is hoped to obtain some idea of the contribution of these metabolic reactions in increasing or decreasing the toxicity of the compound. It is only by knowing the mechanism of toxicity that an intelligent approach to eliminating or, at least, decreasing toxic hazards can be undertaken.
NIH ExPorter
NIH ExPorter