Bt Research 2015, Vol.6, No.4, 1-12
6
highest level of exotoxin (2.5 mg) killed 100% of
individuals in 7 days. Sharma and Sahu (1977) performed
tests with root meristem cells of
Allium cepa
(onion)
and report that thuringiensins are able to inhibit spindle
and cytokinesis and induces micronuclei, and minor in
spindle activity. According to the authors, the binucleated
cells also undergo mitosis giving biprophases and
bimetaphases. Finally, they claim that microtubule
systems and chromosomes are implicated as primary
targets of this exotoxin.
6 Toxicity to Mammals
The proven effects of thuringiensins on vertebrates
support the realization of safety tests in mammals,
including toxicity and mutagenicity assays with
intravenous, subcutaneous and intraperitoneal injections;
cultures with human lymphocytes and allergenicity
testing. Several tests using cultures of human blood
and bone marrow cells are evaluated in the cytological
effects after
in vitro
treatment with acute and chronic
exposures of thuringiensins (Meretoja et al., 1977).
The toxicity to mammals was reported by several
authors (Bishop and Robinson 2014; Robacker et al.,
2000; Tsai et al., 2006). From these studies, it is
possible to infer that there is a considerable difference
in the toxicity of thuringiensins in insects and mammals.
According (Vankova et al., 1974), the median lethal
dose (LD50) in rats is 30 times higher than for
Galleria mellonella
larvae (Lepidoptera: Pyralidae). In
high concentrations, thuringiensins are able to cross
the cellular and nuclear membranes in mammalian
systems, and have been reported neurotoxic, mutagenic
and teratogenic effects in rats treated with these
exotoxins (Meretoja et al., 1977).
Injections of lethal amounts of thuringiensins (10 ml /
kg) can cause liver disorders, cellular degeneration
and necrosis, hemorrhage and hepatic steatosis in mice
(Meretoja et al., 1977). According to (Meretoja et al.,
1977), human blood cultures treated with toxic
concentrations of thuringiensins showed a significant
increase in the incidence of chromosomal aberrations.
Clastogenic effects have also been reported in bone
marrow of rats that ingested thuringiensin for a month,
or animals that received lethal doses of the toxin,
much higher than the amounts normally used for
control of insect pests. (Tsai et al., 2004) evaluated the
effect of thuringiensins on the activity of the enzyme
adenylate cyclase in the cerebral cortex of rats. The
authors observed that the exotoxin is able to activate
the enzyme and it may disturb cAMP-mediated signal
transduction (adenosine 3' 5' - monophosphate), which
is an important mediator of the action of various
physiological functions in neuroendocrine systems.
The effect of thuringiensins by intratracheal instillation
in rats induces pulmonary emphysema, fibrosis and
death (Tsai et al., 1998). (Tsai et al., 2003) reported
that intratracheal instillation thuringiensins results in
highly inflammatory effect with a significant infiltration
of polymorphonuclear neutrophils, which can lead to
neurological disorders and damages to the cells of
terminal bronchioles in the lung, in addition display
fibrotic properties, due to accumulation of collagen.
According to (Tsai et al., 2006), the intratracheal
instillation of thuringiensin by rats resulted in lung
damage, such as increase in weight; alkaline phosphatase
decrease; lipid peroxidation increased; decrease in the
activities of superoxide dismutase and glutathione;
release of pro-inflammatory cytokines; excessive
production of oxidants and may induce the lethality in
some animals.
However, when dephosphorylated enzymatically or
chemically, thuringiensins become biologically inactive
(Bond et al., 1969). So when this toxin is ingested by
mammals via gastrointestinal tract, can occur enzymatic
dephosphorylation, which finishes with the toxicity of
the molecule (Šebesta et al., 1981; Šebesta and Horska
1970). This could explain the lack of effects in the
liver of rats treated with thuringiensins to long-term
(Meretoja et al., 1977); the excretion of thuringiensin
in the unchanged form in the urine of rats treated with
the toxin via intraperitoneal; or the non-cumulation of
the exotoxin in mice tissues (Šebesta and Horska,
1970). Corroborating this, (Šebesta et al., 1981), (Tsai
et al., 2003) and (Vankova et al., 1974) stated that
thuringiensin is more toxic when administered by
intraperitoneal route than orally.
Although many studies have proven the harmfulness
of thuringiensins when administered at high doses,
there are also reports that expose his harmlessness in
low doses. Carlberg (1973) demonstrated that feeding
rats with thuringiensin for a long period, not presented
pathological differences between the treated animals
