Different sensitivity of two Walker 256 carcinoma lines to cyclophosphamide

Correlation with drug distribution, biotransformation and macromolecule binding

M. G. Donelli, A. Guaitani, L. Torti, G. Damia, F. Corti, M. Bianchi, M. Tortoreto, C. Pantarotto, I. Bartosek

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Two closely related lines of the same Walker 256 carcinoma in Crl-CD/COBS rats, described as behaving differently as regards tumor growth and host reaction, show different chemotherapeutic sensitivity to cyclophosphamide (CPA). Line B, which induces early cachexia with marked anorexia, is only moderately sensitive to CPA, while line A, which causes mild anorexia and only terminal cachexia, shows marked responsiveness to CPA, cure being attained in 75% of animals treated with a single dose of 120 mg/kg and in 90-100% of those given 20 mg/kg every other day. Comparative studies in both tumor lines on the distribution of CPA in vivo and on its metabolism by the liver perfusion technique showed no appreciable differences between the two lines in the pharmacokinetics of the compound, but indicate a much greater metabolizing capacity of CPA in the Walker 256/A animals. In vitro metabolic and covalent binding studies confirm that the liver of the Walker 256/A group metabolizes and covalently binds twice as much CPA as the liver of the Walker 256/B group. Conversely to Walker B, microsomal preparations of the Walker tumor line A are able to metabolize CPA to intermediates which irreversibly bind to tissue macromolecules, suggesting an in situ activation of the compound in the sensitive Walker tumor.

Original languageEnglish
Pages (from-to)257-263
Number of pages7
JournalOncology
Volume43
Issue number4
Publication statusPublished - 1986

Fingerprint

Walker Carcinoma 256
Biotransformation
Cyclophosphamide
Pharmaceutical Preparations
Cachexia
Anorexia
Liver
Neoplasms
Pharmacokinetics
Perfusion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Different sensitivity of two Walker 256 carcinoma lines to cyclophosphamide : Correlation with drug distribution, biotransformation and macromolecule binding. / Donelli, M. G.; Guaitani, A.; Torti, L.; Damia, G.; Corti, F.; Bianchi, M.; Tortoreto, M.; Pantarotto, C.; Bartosek, I.

In: Oncology, Vol. 43, No. 4, 1986, p. 257-263.

Research output: Contribution to journalArticle

Donelli, MG, Guaitani, A, Torti, L, Damia, G, Corti, F, Bianchi, M, Tortoreto, M, Pantarotto, C & Bartosek, I 1986, 'Different sensitivity of two Walker 256 carcinoma lines to cyclophosphamide: Correlation with drug distribution, biotransformation and macromolecule binding', Oncology, vol. 43, no. 4, pp. 257-263.
Donelli, M. G. ; Guaitani, A. ; Torti, L. ; Damia, G. ; Corti, F. ; Bianchi, M. ; Tortoreto, M. ; Pantarotto, C. ; Bartosek, I. / Different sensitivity of two Walker 256 carcinoma lines to cyclophosphamide : Correlation with drug distribution, biotransformation and macromolecule binding. In: Oncology. 1986 ; Vol. 43, No. 4. pp. 257-263.
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abstract = "Two closely related lines of the same Walker 256 carcinoma in Crl-CD/COBS rats, described as behaving differently as regards tumor growth and host reaction, show different chemotherapeutic sensitivity to cyclophosphamide (CPA). Line B, which induces early cachexia with marked anorexia, is only moderately sensitive to CPA, while line A, which causes mild anorexia and only terminal cachexia, shows marked responsiveness to CPA, cure being attained in 75{\%} of animals treated with a single dose of 120 mg/kg and in 90-100{\%} of those given 20 mg/kg every other day. Comparative studies in both tumor lines on the distribution of CPA in vivo and on its metabolism by the liver perfusion technique showed no appreciable differences between the two lines in the pharmacokinetics of the compound, but indicate a much greater metabolizing capacity of CPA in the Walker 256/A animals. In vitro metabolic and covalent binding studies confirm that the liver of the Walker 256/A group metabolizes and covalently binds twice as much CPA as the liver of the Walker 256/B group. Conversely to Walker B, microsomal preparations of the Walker tumor line A are able to metabolize CPA to intermediates which irreversibly bind to tissue macromolecules, suggesting an in situ activation of the compound in the sensitive Walker tumor.",
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