, Volume 16, Issue 2, pp 131–136 | Cite as

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

  • Andrew G. Bosanquet
  • Alison R. Burlton
Technical Report


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 forin 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.

Key words

Treosulfan busulphan airborne cytotoxicity in vitro assays DiSC assay 



acute lymphoblastic leukaemia


acute non-lymphocytic leukaemia


chronic lymphocytic leukaemia


non-Hodgkin's lymphoma

DiSC assay

differential staining cytotoxicity assay

MTT assay

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay


phosphate buffered saline


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bird MC, Bosanquet AG, Forskitt S and Gilby ED (1986) Semimicro adaptation of a 4-day differential staining cytotoxicity (DiSC) assay for determing thein vitro chemosensitivity of haematological malignancies. Leuk. Res. 10:445–449.Google Scholar
  2. Blomgren H and Hallström M (1989) Release of a volatile factor from solutions of oxazaphosphorines which damage normal and malignant cells. Meth. Find. Exp. Clin. Pharmacol. 11:391–397.Google Scholar
  3. Bosanquet AG (1991) Correlations between therapeutic response of leukaemias andin vitro drug-sensitivity assay. Lancet 337: 711–714.Google Scholar
  4. Bosanquet AG (1993)In vitro drug sensitivity testing for the individual patient: an ideal adjunct to current methods of treatment choice. Clin. Oncol. 5:195–197.Google Scholar
  5. Bosanquet AG (1994) Short-termin vitro drug sensitivity tests for cancer chemotherapy. A summary of correlations of test result with both patient response and survival. Forum Trends Exp. Clin. Med. 4:42–58.Google Scholar
  6. Boullier AB and Bosanquet AG (1990) Reduced cell viabilityin vitro following exposure to a routine laboratory disinfectant. Cytotechnology 4:109–110.Google Scholar
  7. Copelan EA (1992) Conditioning regimens for allogenic bone marrow transplantation. Hematol. Oncol. 6:234–242.Google Scholar
  8. Feit PW and Rastrup-Anderson N (1973) 4-Methanesulfonyloxybutanol: Hydrolysis of Busulfan. J. Pharm. Sci. 62:1007–1008.Google Scholar
  9. Feit PW, Rastrup-Anderson N and Matagne R (1970) Studies on epoxide formation from (2S,3S)-threitol 1,4-bismethanesulfonate. The preparation and biological activity of (2S,3S)-1,2-epoxy-3,4-butanediol 4-methanesulfonate. J. Med. Chem. 13:1173–1175.Google Scholar
  10. Fruehauf JP and Bosanquet AG (1993)In vitro determination of drug response: a discussion of clinical applications. In: DeVita VT, Hellman S and Rosenberg SA (eds), Cancer Principals and Practice of Oncology, PPO updates. Philadelphia Lippincott. Vol 7 (Part 12):1–16.Google Scholar
  11. Hassan M and Ehrsson H (1986) Degradation of busulfan in aqueous solution. J. Pharm. Biomed. Anal. 4:95–101.Google Scholar
  12. Koeffler HP and Golde DW (1990) Chronic Myelogenous Leukemia. In: Haskell CM (ed), Cancer Treatment. 3rd Edition. Philadelphia: Saunders. pp. 620–627.Google Scholar
  13. Lelieveld P, Aapro MS, van Lambalgen R and van den Berg KG (1986) Sodium azide is less suitable as a positive control of drug-induced lethality forin vitro clonogenic assays. Invest New Drugs 4:367–371.Google Scholar
  14. Masding J, Sarkar TK, White WF, Barley VL, Chawla SL, Rostom AY and Menday AP (1990) Intravenous treosulfan versus intravenous treosulfan plus cisplatinum in advanced ovarian carcinoma. Br. J. Obstet. Gynaecol. 97:342–351.Google Scholar
  15. Wilson JK, Sargent JM, Elgie AW, Hill JG and Taylor CG (1990) A feasibility study of the MTT assay for chemosensitivity testing in ovarian malignancy. Br. J. Cancer 62:189–194.Google Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Andrew G. Bosanquet
    • 1
    • 2
  • Alison R. Burlton
    • 1
  1. 1.Bath Cancer Research UnitRoyal United HospitalBathUK
  2. 2.School of Postgraduate MedicineUniversity of BathBathUK

Personalised recommendations