TY - JOUR
T1 - Development and characterization of a cyclophosphamide-resistant mouse plasmacytoma cell line
AU - Frondoza, C. G.
AU - Trivedi, S. M.
AU - Humphrey, R. L.
PY - 1982
Y1 - 1982
N2 - Murine LPC-1 plasmacytoma is sensitive to treatment with cyclophosphamide (CY), and 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, we have developed from this CY-sensitive parent line (CY-S) a stable CY-resistant subline (CY-R) that is unaffected by doses as large as 250 mg/kg. Stability of this induced CY resistance in the absence of CY treatment has been demonstrated for > 14 transfer generations. The CY-R subline has been compared to the CY-S parent line and shown to be similar with respect to morphology, growth kinetics, survival time, synthesis of IgG 2ak 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) was tested, and 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.
AB - Murine LPC-1 plasmacytoma is sensitive to treatment with cyclophosphamide (CY), and 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, we have developed from this CY-sensitive parent line (CY-S) a stable CY-resistant subline (CY-R) that is unaffected by doses as large as 250 mg/kg. Stability of this induced CY resistance in the absence of CY treatment has been demonstrated for > 14 transfer generations. The CY-R subline has been compared to the CY-S parent line and shown to be similar with respect to morphology, growth kinetics, survival time, synthesis of IgG 2ak 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) was tested, and 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.
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M3 - Article
C2 - 7093969
AN - SCOPUS:0019973103
SN - 0361-5960
VL - 66
SP - 1535
EP - 1544
JO - Cancer treatment reports
JF - Cancer treatment reports
IS - 7
ER -