| Summary: | <p>T-2 toxin, a trichothecene mycotoxin produced by some Fusarium fungi,
is possibly the cause of several mycotoxicoses of humans and livestock.
Several studies were conducted to characterize the "dermatitic" and the
"radiomimetic" properties of T-2 toxin, and to determine their effects on
animals fed T-2 toxin in the diet.</p>
<p>The dermatitic responses to T-2 toxin and a similar trichothecene,
diacetoxyscirpenol (DAS), were examined by applying the toxins to the skin
of rats. The resulting acute non-specific dermal inflammatory reactions
were, at all stages of development, histologically similar to reactions
produced by croton oil. The skin of rabbits treated with T-2 toxin reacted
in the same way.</p>
<p>Variation in sensitivity among rats was responsible for poor correlation
between dose and visible signs of cutaneous inflammation, measured either
by subjective rating of the intensity of inflammation, or by frequency-response.
However, variation in sensitivity among test rats had little
influence on the dose-response relationship when reactions were rated in
units of equivalent concentration of T-2 toxin by comparison with reactions
to a graded series of standard solutions of T-2 toxin applied to the same
rat. This novel method of evaluating reactions improved the skin-irritation
bioassay for trichothecenes such that test solutions in the range of 5 to
60 pg/ml were measured accurately and precisely to within 13% of actual
concentrations.</p>
<p>Intragastric administration of a single sublethal dose of T-2 toxin
(2.0 or 2.5 mg/kg) to juvenile Swiss mice caused necrosis of lymphoblasts
in lymphoid follicles, of lymphocytes in the intestinal mucosa, of
lymphocytes in the thymic cortex, of epithelial cells in intestinal crypts,
and of hematopoietic cells in splenic red pulp and bone marrow within 6
hours. The severity of injury in these tissues was dose-dependent.
Ultrastructurally and histologically, lesions resembled those reported in
response to various anti-neoplastic chemicals. Cells in damaged target
tissues regenerated during a 96-hour period after treatment.</p>
<p>The subacute toxic effects of dietary T-2 toxin on the hematopoietic,
lymphopoietic, and alimentary systems were examined in Swiss mice and Wistar
rats. Attempts were made to identify factors that potentiated the toxicity
of dietary T-2 toxin to the hematopoietic system. Dietary T-2 toxin at levels
of 10 or 20 ppm, in either natural-ingredient diets or in semipurified diets
of various protein levels, consistently caused dose-dependent thymic atrophy,
lymphopenia, gastric hyperkeratosis and gastric ulceration in juvenile mice.
Similar, but less severe effects occurred in adult mice and in young rats fed
these levels of T-2 toxin in natural-ingredient diets. Juvenile mice fed
20 ppm of T-2 toxin also developed aplastic anemia due to suppression of
erythropoiesis in splenic red pulp and in bone marrow. Hypoplastic
hematopoietic and lymphopoietic tissues began to regenerate within 7 days
in mice transferred from toxic diets to control diets.</p>
<p>Suppression of hematopoiesis in juvenile mice fed T-2 toxin was
probably a subacute manifestation of the toxicity of T-2 toxin to rapidly
dividing cells. This effect was transient during continuous dietary
exposure because suppression was gradually overcome and hematopoietic cells
regenerated after several weeks. Such recovery may have been due to
biotransformation of T-2 toxin into a non-toxic metabolite by the liver
because recovery occurred more slowly in.mice housed in suspension cages
than in mice housed on softwood bedding, a known inducer of microsomal
enzyme activity. Perioral dermatitis, gastritis, and hyperplasia of the
gastric and duodenal mucosa, all of which were attributed to direct
irritant toxicity of T-2 toxin to the upper alimentary tract, persisted
in mice that overcame the suppression of hematopoiesis. Thus, mice
eventually exhibited similar toxic effects as were observed in rats, and
as have been reported in swine and poultry fed dietary T-2 toxin. Diets
of low protein content (8%) potentiated the toxicity of dietary T-2 toxin
to juvenile mice by prolonging the period of suppression of hematopoiesis
and lymphopoiesis. These results supported the hypothesis that the normally
low susceptibility of animals to the hematopoietic-suppressive or immunosuppressive
effects of dietary T-2 toxin is increased under conditions of
suboptimal protein nutrition.</p>
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