Airborne cytotoxicity in the DiSC assay caused by solutions of treosulfan but not busulphan

Abstract

Treosulfan and busulphan are similar molecules, the former used in the treatment of ovarian cancer and the latter in chronic myelogenous leukaemia. We have used both in the differential staining cytotoxicity (DiSC) assay for in vitro drug sensitivity testing to aid in the choice of chemotherapy for individual patients. It was observed that occasionally the viability of control cells in one assay box was reduced compared with control cells in other boxes from the same assay. Treosulfan was suspected as the cause because cells throughout the microtitre box containing treosulfan had reduced viability in 28/62 (45%) experiments and in 9 of these, total kill of all cells in the box was observed. We tested the hypothesis that a metabolite of treosulfan might be the cause of this airborne cytotoxicity, and found that whilst 10 mg ml-1 of either methane sulphonic acid or tetrahydrofuran had no airborne cytotoxic effect, 1 mg ml-1 diepoxybutane killed over 95% of cells in all tubes in the same box. Treosulfan is another chemical (cf. azide, mafosfamide and possibly other cytotoxic agents) that can cause airborne cytotoxicity.

Cytotoxicity of treosulfan and busulfan on pediatric tumor cell lines

“…1) [27]. In addition, diepoxybutane is volatile and was reported to cause airborne cytotoxicity of treosulfan in vitro.…”