Induction of heat shock protein 70 in rat olfactory epithelium by toxic chemicals: in vitro and in vivo studies.
We have previously developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to determine whether heat shock protein (HSP) 70 is induced in this model following exposure to carbon tetrachloride (CCl4), dimethyl adipate (DMA), methyl iodide (CH3I) or paracetamol, and whether HSP70 can also be induced in the nasal cavity in vivo. Intracellular ATP was significantly depleted in ethmoturbinates incubated for 4 h with the toxins (0-100 mM; EC50 concentrations: CCl4 32 mM, DMA 3 mM, CH3I 1.5 mM, paracetamol 70 mM), but there was little induction of HSP70. Turbinates were then incubated for 1 h with CCl4 (5 mM), DMA (1.5 mM), CH3I (0.57 mM) or paracetamol (30 mM) and allowed to recover for up to 24 h. Treatment with CCl4, DMA or paracetamol resulted in 250-300% induction of HSP70. Male rats were administered a single oral dose of CCl4 (1600 mg/kg) and killed 16 h later. Degenerative lesions (epithelial undulation and hydropic vacuolation) were evident in the olfactory epithelium, and immunohistochemical analysis of HSP70 revealed increased staining in, or proximate to, areas of damage. Thus, HSP70 can be induced in the olfactory epithelium both in vitro and in vivo.
Simpson
S A
SA
School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
Alexander
D J
DJ
Reed
C J
CJ
D000082:Acetaminophen / Q000633:toxicity; D000255:Adenosine Triphosphate / Q000378:metabolism; D000272:Adipates / Q000633:toxicity; D018712:Analgesics, Non-Narcotic / Q000633:toxicity; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000272:Adipates; D018712:Analgesics, Non-Narcotic; D018840:HSP70 Heat-Shock Proteins; D000082:Acetaminophen; C067354:dimethyladipate; D000255:Adenosine Triphosphate