A synthetic antisense oligodeoxyribonucleotide with sequence complementary to the messenger RNA (mRNA) coding for human metallothionein (MT) II was prepared and tested for its ability to inhibit both constitutive- and cadmium-induced MT protein synthesis in neuroblastoma-IMR and Chang liver cells in culture. The sense oligonucleotide was also prepared and tested as a control for its sequence-specific effects. Oligonucleotide entry into cells was enhanced through the use of a polybrene carrier so that nearly 30% of a 10 µM dose of oligonucleotide was shown to be associated with cells. The antisense oligonucleotide inhibition of MT protein synthesis rendered both cell types more sensitive to cadmium toxicity. However, the sense oligonucleotide had no effects on either MT protein synthesis or sensitivity to cadmium toxicity.

Keywords:
Metallothionein, Neuroblastoma IMR32, Chang liver cells, Cadmium, Zinc, Antisense oligonucleotide
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© 1992 S. Karger AG, Basel
1992
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