Binding of oxamniquine to the DNA of schistosomes.
Hycanthone-sensitive and hycanthone-resistant schistosomes (which are also sensitive and resistant to oxamniquine) were exposed in vitro to tritium-labelled oxamniquine. The initial uptake of the drug into the schistosomes was essentially the same for the 2 strains. The homogenate of worms incubated with tritiated oxamniquine was fractionated and a purified DNA fraction was obtained by ethanol precipitation, RNAase and protease digestion, repeated phenolchloroform extractions, CsC1 gradient centrifugation and extensive dialysis. The DNA fraction from sensitive worms contained radioactive oxamniquine at a level corresponding to about 1 drug molecule per 50,000 base pairs, while the DNA from resistant worms contained essentially no drug. The results support the hypothesis that oxamniquine, like hycanthone, exerts its activity by alkylating macromolecules of sensitive schistosomes. The possibility is discussed that oxamniquine may lack the mutagenic properties of hycanthone because it is not an intercalating agent.[1]References
- Binding of oxamniquine to the DNA of schistosomes. Pica-Mattoccia, L., Cioli, D., Archer, S. Trans. R. Soc. Trop. Med. Hyg. (1989) [Pubmed]
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