CYTOSINE-ARABINOSIDE IS NEUROTOXIC TO CHICK-EMBRYO SPINAL-CORD MOTONEURONS IN CULTURE

Cytosine arabinoside (1-beta-D-arabinofuranosylcytosine, AraC) is a co mmonly used antimitotic agent that kills proliferating cells by inhibi ting DNA synthesis. We report that AraC is toxic to cultured chick emb ryo spinal cord motoneurons (MTNs) in a concentration-dependent fashio n with an EC(50) of about 2 mu M. Interestingly, this type of MTN deat h is specific, resembles that occurring upon muscle extract (MEX) trop hic deprivation regarding its morphological and temporal characteristi cs, and has apoptotic features, as judged by observation of nuclear mo rphology. The death of AraC-treated MTNs can be blocked by 2'-deoxycyt idine (dC), a pyrimidine metabolite AraC is structurally related to. O verall, these findings suggest that dC may participate in a pathway, d ifferent from inhibition of DNA synthesis, that is necessary for cultu red MTNs to respond to the trophic activities present in MEX. (C) 1997 Elsevier Science Ireland Ltd.