DEVELOPMENT AND CHARACTERIZATION OF A CYCLOPHOSPHAMIDE-RESISTANT MOUSE PLASMACYTOMA CELL-LINE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 66  (7) , 1535-1544
Abstract
Murine LPC-1 plasmacytoma is sensitive to treatment with cyclophosphamide (CY); animals bearing this tumor in advanced stages can be cured with doses as small as 60 mg/kg. With repeated transfer of LPC-1 cells followed by subcurative CY therapy, a stable CY-resistant subline (CY-R) that is unaffected by doses as large as 250 mg/kg was developed from this CY-sensitive parent line (CY-S). Stability of this induced CY resistance in the absence of CY treatment was demonstrated for > 14 transfer generations. The CY-R subline was compared to the CY-S parent line and was similar with respect to morphology, growth kinetics, survival time, synthesis of IgG 2a.kappa. M component and DNA content and distribution. The CY-S parent line responds in vivo to CY analogs (ifosfamide and trofosfamide), as judged by decreased tumor mass and increased survival; the CY-R subline is resistant to the CY analogs. The response to carmustine (BCNU [1,3-bis-(2-chloroethyl)-1-nitrosourea]) was test; resistance to CY did not predict for response to this alkylating agent since the effect on both CY-S and CY-R lines was equal. The significance of the development of this CY-resistant subline and the implications for future research into the mechanisms of such resistance are discussed.