Hexachlorobenzene (
HCB) is a widespread
environmental pollutant. Chronic exposure of humans to
HCB produces a number of effects, such as triggering of
porphyria, increased synthesis of liver microsomal
enzymes, neurological symptoms, immunological disorders and thyroid dysfunctions. In rats,
HCB induced
hepatic porphyria, neurotoxic effects, and toxic effects on the reproductive system, thyroid function, and immune system.
HCB is also known to cause
tumors of the liver, thyroid and mammary gland in laboratory animals. The aim of this study was to investigate parameters of thyroid growth regulation, mainly cell proliferation and apoptosis in thyroid tissue from
HCB (0.1, 1, 10, 100, and 500 mg/kg
body weight)-treated female Wistar rats. The current study demonstrates that only the exposure to the highest
HCB dose for 30 days, has adverse effects on thyroid endpoints examined related to thyroid gland morphology, and 3,3'5,5'-tetraiodothyronine (T(4),
thyroxine) serum levels, without changes in
thyroid-stimulating hormone concentrations or in thyroid gland weight. Morphological changes, included flattened epithelium and increased
colloid size compared with control tissue.
Transforming growth factor (TGF-beta1)
mRNA levels, evaluated by RT-PCR, revealed a significant upregulation after exposure to
HCB (1, 10, 100 mg/kg
body weight). Cell proliferation evaluated by 5'-Br deoxiuridine incorporation into
DNA, was not altered at any dose.
HCB (1, 10, 100 mg/kg
body weight) induces apoptosis, evaluated by in situ end labeling of fragmented
DNA,
terminal deoxynucleotidyl transferase-mediated deoxy
uridine triphosphate nick-end labeling, in rat thyroid glands. This process is associated with dose-dependent increases in
cytochrome c release from the mitochondria and
procaspase-9 processing to its active product.
Caspase-8 was not activated. These studies indicate that doses of
HCB that do not disrupt thyroid economy induce
TGF-beta1 expression and apoptosis in the thyroid gland, involving the mitochondrial pathway.