MALTOL (3-HYDROXY-2-METHYL-4-PYRONE) TOXICITY IN NEUROBLASTOMA CELL-LINES AND PRIMARY MURINE FETAL HIPPOCAMPAL NEURONAL CULTURES

Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degrad ation, is known to enhance aluminium-induced neurofibrillary degenerat ion in neuronal systems, but few toxicological studies have been condu cted. We report maltol toxicity in neuroblastoma cell lines of mouse ( Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippo campal neuronal cultures. As determined by MTS imethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt ] conversion, maltol exhibited a dose-dependent toxicity on the viabil ity of both neuroblastoma cell lines, but the toxicity was more pronou nced in Neuro 2a cells. Maltol was also toxic in a dose-dependent mann er in primary murine fetal hippocampal neurons at micromolar concentra tions. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apoptotic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends wer e visualized in situ in morphologically condensed nuclei by terminal d eoxynucleotidyl transferase with digoxigenin-labelled UTP and subseque nt immunohistochemistry. Collectively, our findings suggest that the t oxic effect of maltol is mediated through apoptosis. Further toxicolog ical investigations are warranted, since maltol is found in the daily diet of humans. (C) 1996 Academic Press Limited