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Induction of S 100 Protein by 5-Bromo-2'-deoxyuridine in Human Neuroblastoma Cell Lines

Department of Pediatrics and Children's Research Hospital, Kyoto Prefectural University of Medicine, Kawaramachi, Kamikyo-ku, Kyoto 602, and Department of Biochemistry, Institute for Development Research, Aichi Prefectural Colony, Kamiya, Kasugai, Aichi 480-03, Japan

The simultaneous effect of 5-bromo-2'-deoxyuridine (BrdUrd) on cell growth, morphological changes, and cellular contents of S 100 (S 100a₀ 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 µg/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 100a₀ protein was increased from 37 to 211,000 pg/mg protein (5,600-fold) and S 100b protein from <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.

¹ To whom requests for reprints should be addressed.

Received 2/25/87. Revised 8/25/87. Accepted 9/30/87.

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