Biomedical subjects

S Darkin

Publications and source records attributed to S Darkin.

4 recordsLinked to original sources

PubMed1986

Potentiation of 4'-(9-acridinylamino)methanesulphon-m-anisidine) action by verapamil.

Verapamil was shown to increase growth inhibition and decrease viability of PY815 mastocytoma cells treated with the anti-cancer drug mAMSA 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA) or its normally inactive congener, 4'-(9-acridinylamino)methanesulphon-o-anisidide (oAMSA). Verapamil also potentiated the effect of sub-optimal concentrations of mAMSA or oAMSA on DNA scission in intact cells. Uptake of [14C]mAMSA by PY815 cells was considerably enhanced, while efflux of [14C]mAMSA from precharged cells was inhibited by verapamil. It is concluded that verapamil potentiates the action of mAMSA on PY815 cells in culture by reducing efflux of drug from the cells. The possibility that verapamil may affect systems that sequester or metabolize AMSA drugs is suggested.

Aminoacridines↗

PubMed1985

Transport of AMSA drugs into cells.

The uptake and efflux of radioactive 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA) and its inactive congener 4'-(9-acridinylamino)methanesulphon-o-anisidide (oAMSA) by PY815 mastocytoma cells were investigated. Both drugs were readily taken up by intact cells although only mAMSA caused DNA scission and is actively cytotoxic to PY815 cells. The microsomal enzyme inhibitors cimetidine or SKF525A increased drug uptake and decreased drug efflux suggesting that drug metabolism could explain the different activities of oAMSA and mAMSA.

Aminoacridines↗

PubMed1984

Chlorpromazine: a potential anticancer agent?

The antipsychotic drug chlorpromazine causes scission of the DNA in PY815 mouse mastocytoma cells or isolated PY815 cell nuclei and the broken DNA reseals when chlorpromazine is removed from nuclei. These properties suggest that chlorpromazine interferes with topoisomerase action as do several other DNA-intercalating anti-cancer drugs. However, protein is not associated with the broken DNA after chlorpromazine treatment suggesting a different mode of action on the topoisomerase. Reasons why chlorpromazine may have potential as anti-cancer agent are considered.

Aminoacridines↗

PubMed1983

Evidence that mAMSA induces topoisomerase action.

Evidence is presented that the topoisomerase inhibitors novobiocin and coumermycin inhibit the production of double-strand breaks in mouse mastocytoma cell nuclear DNA by the anticancer drug 4'[(9-acridinyl)amino]-methanesulphon-m-anisidide (mAMSA). Novobiocin did not inhibit resealing of DNA breaks induced by mAMSA. It is suggested that mAMSA intercalation into DNA induces the action of a type II topoisomerase. mAMSA and oAMSA were equally effective in breaking the DNA in isolated nuclei.

Aminoacridines↗