Induction of S 100 protein by 5-bromo-2'-deoxyuridine in human neuroblastoma cell lines

The simultaneous effect of 5-bromo-2'-deoxyuridine (BrdUrd) on cell growth, morphological changes, and cellular contents of S 100 (S 100ao and S 100b) protein and neuron specific enolase was investigated in human neuroblastoma cells in culture. Among four cell lines (NCG, SK-N-DZ, GOTO, NB-1), GOTO was the most affected. With 5 micrograms/ml BrdUrd, the growth of this cell line was significantly inhibited to 14.5% of the control on day 6, in association with morphological changes into flat-type cells and an increase of S 100 protein. S 100ao protein was increased from 37 to 211,000 pg/mg protein (5,600-fold) and S 100b protein from less than 25 to 623 pg/mg protein. The induction of S 100 protein was also seen in SK-N-DZ but not in NCG and NB-1. In GOTO the induction of S 100 protein occurred in a dose- and time-dependent manner by the treatment with BrdUrd. On the other hand, after exposure to BrdUrd, neuron specific enolase decreased in NB-1 and SK-N-DZ and increased in GOTO. These results suggest that although heterogeneous certain neuroblastoma cell lines could be differentiated into S 100 protein-positive cells that may represent glial or Schwann cells and that the effect of BrdUrd is exerted bidirectionally in neuroblastoma differentiation.