Following abstracts describe TCDD's affect on intestines of monkeys,
mice and worms.
Toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF)
in the rhesus monkey (Macaca mulatta).
The toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran
(4PeCDF), a ubiquitous and acutely toxic environmental contaminant,
was examined in three adult male Rhesus monkeys administered a single
iv dose of 34 micrograms (0.1 mumol)/kg. Within 20 min, 4PeCDF was
eliminated from the blood and was distributed to the liver, skin,
adipose, and muscle tissues. Excretion occurred primarily via the
feces with a minimum whole body half-life approximately 38 days.
Within 7-14 days after administration, the packed cell volume and
serum triglyceride and bile acid concentrations were significantly
increased while serum cholesterol, protein, and albumin concentrations
were decreased relative to pretreatment levels. Thyroid hormone levels
were also altered with an increase in TSH and a decrease in T3 and T4
concentrations. After 28 days, two monkeys began exhibiting alopecia,
hyperkeratinization of the toe and finger nails, facial chloracne-like
lesions, and loss of body weight. They subsequently died 40 and 48
days after treatment. Similar symptoms of toxicity were observed in
the third animal 58 days after 4PeCDF administration, but this animal
appeared to fully recover and was administered 4PeCDF orally and
[3H]1,2,3,7,8-pentachloro-dibenzofuran (1PeCDF) dermally 238 days
after the initial iv dose. In this animal, approximately 2% of an oral
dose of [14C]-4PeCDF was absorbed from the stomach and small intestine
in 6 hr and was distributed mainly to the muscle and skin and less
than 99% of a dermal dose of 1PeCDF remained at the site of
application. Pathological findings in the monkeys that died indicated
hyperplastic and metaplastic changes in the gastric mucosa, the
Meibomian glands of the eyelid, and the ceruminous glands of the ear.
Regression of these lesions was present in the surviving animal.
Therefore, 4PeCDF produces dioxin-like toxicity in the monkey similar
to that re****ted for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and in
the same dose range. PMID: 3358261
=46rom www.springerlink.com/content/p40740546711867n/
Breakdown of mucosal immunity in gut by dioxin (TCDD)
Abstract
Objectives Mucosal immunity plays a pivotal role for body defense
against infection and allergy. The aim of this study was to clarify
the effects of 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD) on mucosal
immunity in the gut.
Methods Fecal IgA level and oral tolerance induction were examined in
TCDD-treated mice. Flow cytometric and histological analyses were also
performed.
Results Single oral administration of low dose 2,3,7,8-TCDD resulted
in a marked decrease in IgA secretion in the gut without any effects
on the cellular components of gut-associated lymphoid tissues (GALT)
including Peyer=92s patches (PPs) and mesenteric lymph nodes (LNs).
Decressed IgA secretion by TCDD was not observed in aryl hydrocarbon
receptor (AhR)-deficient mice. Flow cytometric analysis revealed that
IgA B cells in PPs and the mesenteric LNs remained unchanged in the
TCDD-treated mice. An immunofluorescence study also demonstrated that
a significant number of cytoplasmic IgA cells were present in the
lamina propria of the gut in the TCDD-treated mice. Furthermore, oral
tolerance induction by ovalbumin (OVA) was impaired in the TCDD-
treated mice and OVA-specific T cell proliferation occurred in the
peripheral lymphoid tissues including the spleen and LNs.
Conclusions These results suggest that a relatively low dose of TCDD
impairs mucosal immunity in the gut and induces systemic sensitization
by oral antigens.
Apoptosis of the intestinal principal cells of Xenopus larvae exposed
to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
In our previous work using paraffin-embedded sections, we determined
that Xenopus larvae exposed to 200 ppb 2,3,7,8-tetrachlorodibenzo-p-
dioxin (TCDD) for 5 days from shortly after fertilization to the early
larval stage showed a shortening of the digestive tract and a loss of
mucosal epithelium cells due to exfoliation into the gut cavity. In
the current study, we ultrastructurally examined the mucosal
epithelium of the gut of TCDD-exposed Xenopus larvae 12 days after
fertilization. Exfoliated cell structures at the villus tip and in the
lumen were equipped with a microvillus ****tion and occasionally had
terminal web-like structures seen by ultramicroscopy. As these
exfoliated structures had nuclear fragments with condensed chromatin,
they were considered to be apoptotic bodies derived from the principal
cells of the epithelium. In addition, many membrane-bound cell
fragments-identified as apoptotic bodies derived from the principal
cells based on their ultrastructural features-were observed at the
basal side of the mucosal epithelium. These apoptotic bodies were
phagocytized and digested chiefly by the neighboring intact principal
cells. No such cells and/or cell fragments showing apoptotic features
were observed in the controls. Our observations indicate that marked
apoptosis occurs in the intestinal principal cells of TCDD-exposed
larvae, which may result in the shortening of the gut. PMID: 15281239
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