Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells

FLORENCIA CHIAPPINI; LAURA ALVAREZ; VICTORIA LUX-LANTOS; ANDREA RANDI; DIANA KLEIMAN DE PISAREV

TOXICOLOGICAL SCIENCES

OXFORD UNIV PRESS

Año: 2009 vol. 108 p. 301 - 310

1096-6080

Hexachlorobenzene (HCB) is a widespread environmentalpollutant. Chronic exposure of humans to HCB producesa number of effects, such as triggering of porphyria, increasedsynthesis of liver microsomal enzymes, neurological symptoms,immunological disorders and thyroid dysfunctions. In rats, HCBinduced hepatic porphyria, neurotoxic effects, and toxic effects onthe reproductive system, thyroid function, and immune system.HCB is also known to cause tumors of the liver, thyroid andmammary gland in laboratory animals. The aim of this study wasto investigate parameters of thyroid growth regulation, mainly cellproliferation and apoptosis in thyroid tissue from HCB (0.1, 1, 10,100, and 500 mg/kg body weight)–treated female Wistar rats. Thecurrent study demonstrates that only the exposure to the highestHCB dose for 30 days, has adverse effects on thyroid endpointsexamined related to thyroid gland morphology, and 3,3#5,5#-tetraiodothyronine (T4, thyroxine) serum levels, without changesin thyroid-stimulating hormone concentrations or in thyroid glandweight. Morphological changes, included flattened epithelium andincreased colloid size compared with control tissue. Transforminggrowth factor (TGF-b1) 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#-Brdeoxiuridine incorporation into DNA, was not altered at any dose.HCB (1, 10, 100 mg/kg body weight) induces apoptosis, evaluatedby in situ end labeling of fragmented DNA, terminal deoxynucleotidyltransferase-mediated deoxy uridine triphosphate nickendlabeling, in rat thyroid glands. This process is associated withdose-dependent increases in cytochrome c release from themitochondria and procaspase-9 processing to its active product.Caspase-8 was not activated. These studies indicate that doses ofHCB that do not disrupt thyroid economy induce TGF-b1expression and apoptosis in the thyroid gland, involving themitochondrial pathway.