Abstract:
:It is well known that dichlorodiphenyltrichloroethane (DDT) is used as an insecticide and prevents many people in the tropical zone from devastating malaria. On the other hand, a number of reports have indicated that it may act as an endocrine disruptor and also has possible carcinogenic effects. However, the effects of DDT on the neural cells remain to be investigated. In this study, therefore, we observed the effects of p,p'-DDT, o,p'-DDT and its major metabolite p,p'-DDE on the differentiation and survival of PC12 pheochromocytoma cells. After stimulation with nerve growth factor, PC12 cells exhibited remarkable neurite outgrowth, suggesting that neuronal differentiation was induced by this growth factor. p,p'-DDT and o,p'-DDT suppressed this neurite outgrowth dose dependently, and p,p'-DDE also revealed a similar effect but to a lesser extent. Apoptotic cell death was induced within 3-6 h after treatment with p,p'-DDT and o,p'-DDT. Again p,p'-DDE showed a weaker apoptosis-inducing effect. In the organochlorine-treated PC12 cells phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) was upregulated, whereas phosphorylation bands were not detected in any kinases of other MAPK groups such as p38 MAPK and SAPK/JNK. A kinase assay on p44/42 MAPK revealed that the extent of phosphorylation of Elk-1 substrates well correlated with the suppressive effect on neuronal differentiation and apoptosis-inducing activity. These results suggest that p,p'-DDT and o,p'-DDT exerted their effects on neuronal cells by the stimulation of p44/42 MAPK, and p,p'-DDE had less effects than the other two organochlorines.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Shinomiya N,Shinomiya Mdoi
10.1016/s0378-4274(02)00401-0keywords:
subject
Has Abstractpub_date
2003-02-03 00:00:00pages
175-83issue
3eissn
0378-4274issn
1879-3169pii
S0378427402004010journal_volume
137pub_type
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