Effects of macrocyclic trichothecene mycotoxins on the murine immune system.
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 shoed 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Hughes
B J
BJ
Hsieh
G C
GC
Jarvis
B B
BB
Sharma
R P
RP
D000818:Animals; D001772:Blood Cell Count; D055598:Chemical Phenomena; D002621:Chemistry; D004912:Erythrocytes / Q000276:immunology; D007107:Immune System / Q000187:drug effects*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007376:Interleukin-2 / Q000096:biosynthesis; D007518:Isoantibodies / Q000032:analysis; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size; D012717:Sesquiterpenes / Q000633:toxicity*; D014255:Trichothecenes / Q000633:toxicity*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D007518:Isoantibodies; D012717:Sesquiterpenes; D014255:Trichothecenes