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Effects of macrocyclic trichothecene mycotoxins on the murine immune system

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Abstract

Macrocyclic trichothecenes are a class of mycotoxins, some of which exhibit substantial antileukemic properties. These compounds vary in their toxicity by approximately 100 fold and are suspected immunotoxins. We studied 11 of these mycotoxins: roritoxin B, myrotoxin B, roridin A, verrucarin A, 16-hydroxyverrucarin A, verrucarin J, baccharinoid B12, roridin D, roridin E, baccharinoid B4 and baccharinoid B5 for their immunotoxicity in CD-1 mice. An equitoxic dose was prepared in 1% DMSO in saline and administered i.p. at half the LD50. Organ weights, WBC, RBC, differentials of blood cell counts, blastogenesis of splenic lymphocytes in response to concanavalin A (Con A), lipopolysaccharide (LPS), phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and mixed lymphocyte reaction (MLR) were studied on day 4 after administration of each mycotoxin. Organ weights showed significant differences between the controls and the baccharinoids with a decrease in spleen weight in baccharinoid B12 and an increased liver weight in B4 and B5 treated animals. Administration of myrotoxin B, roridin A, verrucarin J and roridin E had total WBC counts statistically different from controls, while mice administered myrotoxin B showed a decrease in numbers of RBC. Differentials of WBC were unremarkable regardless of the mycotoxin. Roritoxin B and baccharinoid B5 increased Con A stimulation of splenic lymphocytes. Roridin A and baccharinoid B12 increased LPS stimulation of splenic lymphocytes while baccharinoid B5 decreased the LPS response. Stimulation of splenic lymphocytes with PHA was significantly increased by roridin A and baccharinoid B5. Stimulation of splenic lymphocytes with PWM was not altered significantly by any mycotoxin. The baccharinoids B12 and B4 showed significant increases of T cell proliferation in the MLR. Antibody production evaluated by the sheep red blood cell (SRBC) hemolytic-plaque assay indicated none of the mycotoxins gave a statistically different response. However, anti-SRBC antibodies evaluated by the enzyme-linked immunosorbent assay, were significantly decreased in mice administered roridin D and E and baccharinoid B5.

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Authors and Affiliations

  1. Toxicology Program, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 84322-5600, Logan, Utah, USA

    B. J. Hughes, G. C. Hsieh, B. B. Jarvis &  R. P. Sharma

  2. Department of Chemistry and Biochemistry, University of Maryland, 20742, College Park, Maryland, USA

    B. B. Jarvis

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  1. B. J. Hughes
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  2. G. C. Hsieh
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  3. B. B. Jarvis
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  4. R. P. Sharma
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Supported in part by Public Health Service grants-ES 07097 and CA 25967.

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Hughes, B.J., Hsieh, G.C., Jarvis, B.B. et al. Effects of macrocyclic trichothecene mycotoxins on the murine immune system. Arch. Environ. Contam. Toxicol. 18, 388–395 (1989). https://doi.org/10.1007/BF01062363

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  • DOI: https://doi.org/10.1007/BF01062363

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