Satomi Mizuhashi, Yuji Ikegaya*, Nobuyoshi Nishiyama and Norio Matsuki
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical
Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033,
Japan
*Corresponding author.ﾊﾊFAX:+81-3-5841-4784
E-mail: ikegaya@tk.airnet.ne.jp
Abstract: We investigated the effect of tributyltin (TBT), an endocrine-disrupting
chemical, on the morphology and viability of cultured rat cortical astrocytes.
Cultured astrocytes exhibited smooth and planiform morphology under normal
conditions. Following exposure to TBT, however, they showed rapid morphological
changes that are characterized by asteriated cell bodies and process formation
in a time- and concentration-dependent manner. Higher concentrations of
TBT produced progressive cell death of the astrocytes. In serum-free medium,
TBT at a concentration as low as 200ﾊnM induced the stellation. Pharmacological
studies revealed that the morphological changes were alleviated by application
of diverse free radical scavengers or antioxidants such as catalase, superoxide
dismutase, Trolox, ascorbic acid and N-acetyl-L-cysteine, suggesting that TBT-induced stellation is caused
by oxidative stress involving free radicals, particularly reactive oxygen
species. Furthermore, we found that the astrocyte stellation was abolished
by treatment with inhibitors of phospholipaseﾊC, mitogen-activated protein
kinase kinase or tyrosine phosphatase. The data suggest that TBT causes
the stellation through intracellular signaling cascades rather than its
non-specific toxicity. These findings provide an important insight for reconciling
the problems in assumed aversive actions of this environmental pollutant
for mammals.
Keywords: Organotin, Tributyltin, Astrocyte, Stellation, Morphology
Copyrightｩ The Japanese Pharmacological Society 2000
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