Hexachlorobenzene alters thyroid morphology and induces TGF-beta 1 expression and apoptosis

LAURA ALVAREZ; FLORENCIA CHIAPPINI; RODOLFO KOLLIKER FRERS; ANDREA RANDI.; DIANA KLEIMAN DE PISAREV

Montreal

Congreso; XI International Congress of Toxicology, ICTXI; 2007

ICTXI

Hexaclorobenzene (HCB) is a very persistant pollutant. Exposure of laboratory animals to HCB induces liver microsomes enzymes, liver and thyroid carcinogenesis and alters thyroid hormone homeostasis. Certain microsomal enzyme inducers lead thyroid-follicular cell hiperplasia, and ultimately thyroid tumors. Transforming Growth factor beta-1 (TGF-beta1) has a crucial role in thyroid homeostasis. To study the effect of HCB on thyroid tissue morphology, and parameters of thyroid growth, female Wistar rats were treated with HCB (0.5, 5, 50 and 500 mg/Kg BW) of 30 days. HCB increased follicle colid area, but did not increase total number of follicular cells, or the number of proliferating cells evaluated by 5´Br-deoxyuridine incorporation. Percentage of apoptotic nuclei evaluated by terminal deoxi-UTP nick-end labeling increased significantly 600, 660, 305 y 280 % in HCB (0.5, 5, 50 and 500) respectively. TGF-beta1 expression (RT-PCR) increased (39 and 32 %, p<0.05) in HCB (50 and 500) respectively. Mitochondrial apoptotic Bax protein level evaluated by Westernblot, increased (181, 300, 268 and 525 %, p<0.05), and antiapoptotic Bcl-2 increased (27, 130, 209 and 118 %, p<0.05) in HCB (0.5, 5, 50 and 500) respectively. To our knowledge this is the first indication that HCB alters TGF-beta 1 expression and induces apoptosis in the thyroid, involving the mitochondrial via These observations may be relevant to the early molecular events involved in the control of thyroid gland mass by HCB.