Characterization of a cis-Diamminedichloroplatinum(II)-resistant Human Ovarian Cancer Cell Line and its use in Evaluation of Platinum Analogues

Brent C. Behrens, Hidetaka Masuda, Karen R. Grotzinger, Jacqueline Whang-Peng, Karen G. Louie, Turid Knutsen, Wilma M. Mckoy, Robert C. Young

Research output: Contribution to journalArticle

493 Citations (Scopus)

Abstract

Human ovarian cancer cell lines with stable cisplatin resistance have been developed by chronic exposure of the parent cisplatin-sensitive A2780 line to increasing concentrations of cisplatin. 2780CP8. 2780CPS (CP8 refers to this cell line's growth in medium containing 8 μM cisplatin) has several clonal cytogenetic abnormalities but lacks homogeneously staining regions or double-minute chromosomes. It has a significantly greater monolayer growth rate, cloning efficiency in agarose, and total glutathione content compared to the A2780 line, but similar activities of several glutathione-dependent enzymes. The 2780cpsnsubline is 7.3-fold resistant to cisplatin compared to the A2780 line, as well as cross-resistant to irradiation and melphalan. It is not cross-resistant to Adriamycin, but this develops with increased cisplatin resistance (14-fold) obtained by further cisplatin exposure of 2780CPS. Of the cisplatin analogues tested which are of current clinical interest, carboplatin, iproplatin, and tetraplatin, only the latter is more cytotoxic than cisplatin in the A2780 and 2780CPSlines. The 2780cps subline is also cross-resistant to these analogues in the relative order carboplatin > iproplatin > tetraplatin (most to least cross-resistant). Treatment of a highly cisplatin resistant cell line (2780CP70) with either melphalan or cisplatin was associated with a significant increase in [3H]thymidine incorporation into DNA in the presence of 10 mM hydroxyurea compared with the parent sensitive cell line which showed essentially no capacity to repair DNA damage by these drugs. A2780 and its cisplatin-resistant cell lines may thus be useful in studying drug resistance mechanisms, in screening new drugs for activity (especially against drug resistant tumors), and in formulating induction and salvage therapies for ovarian cancer.

Original languageEnglish
Pages (from-to)414-418
Number of pages5
JournalCancer Research
Volume47
Issue number2
Publication statusPublished - Jan 1 1987
Externally publishedYes

Fingerprint

Platinum
Ovarian Neoplasms
Cisplatin
Cell Line
ormaplatin
Melphalan
Carboplatin
Glutathione
Salvage Therapy
Preclinical Drug Evaluations
Hydroxyurea
Growth
Drug Resistance
Chromosome Aberrations
Pharmaceutical Preparations
Sepharose
Doxorubicin
Thymidine
DNA Damage
Organism Cloning

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Behrens, B. C., Masuda, H., Grotzinger, K. R., Whang-Peng, J., Louie, K. G., Knutsen, T., ... Young, R. C. (1987). Characterization of a cis-Diamminedichloroplatinum(II)-resistant Human Ovarian Cancer Cell Line and its use in Evaluation of Platinum Analogues. Cancer Research, 47(2), 414-418.

Characterization of a cis-Diamminedichloroplatinum(II)-resistant Human Ovarian Cancer Cell Line and its use in Evaluation of Platinum Analogues. / Behrens, Brent C.; Masuda, Hidetaka; Grotzinger, Karen R.; Whang-Peng, Jacqueline; Louie, Karen G.; Knutsen, Turid; Mckoy, Wilma M.; Young, Robert C.

In: Cancer Research, Vol. 47, No. 2, 01.01.1987, p. 414-418.

Research output: Contribution to journalArticle

Behrens, BC, Masuda, H, Grotzinger, KR, Whang-Peng, J, Louie, KG, Knutsen, T, Mckoy, WM & Young, RC 1987, 'Characterization of a cis-Diamminedichloroplatinum(II)-resistant Human Ovarian Cancer Cell Line and its use in Evaluation of Platinum Analogues', Cancer Research, vol. 47, no. 2, pp. 414-418.
Behrens, Brent C. ; Masuda, Hidetaka ; Grotzinger, Karen R. ; Whang-Peng, Jacqueline ; Louie, Karen G. ; Knutsen, Turid ; Mckoy, Wilma M. ; Young, Robert C. / Characterization of a cis-Diamminedichloroplatinum(II)-resistant Human Ovarian Cancer Cell Line and its use in Evaluation of Platinum Analogues. In: Cancer Research. 1987 ; Vol. 47, No. 2. pp. 414-418.
@article{fb06391a48a549799f11015defbc99bd,
title = "Characterization of a cis-Diamminedichloroplatinum(II)-resistant Human Ovarian Cancer Cell Line and its use in Evaluation of Platinum Analogues",
abstract = "Human ovarian cancer cell lines with stable cisplatin resistance have been developed by chronic exposure of the parent cisplatin-sensitive A2780 line to increasing concentrations of cisplatin. 2780CP8. 2780CPS (CP8 refers to this cell line's growth in medium containing 8 μM cisplatin) has several clonal cytogenetic abnormalities but lacks homogeneously staining regions or double-minute chromosomes. It has a significantly greater monolayer growth rate, cloning efficiency in agarose, and total glutathione content compared to the A2780 line, but similar activities of several glutathione-dependent enzymes. The 2780cpsnsubline is 7.3-fold resistant to cisplatin compared to the A2780 line, as well as cross-resistant to irradiation and melphalan. It is not cross-resistant to Adriamycin, but this develops with increased cisplatin resistance (14-fold) obtained by further cisplatin exposure of 2780CPS. Of the cisplatin analogues tested which are of current clinical interest, carboplatin, iproplatin, and tetraplatin, only the latter is more cytotoxic than cisplatin in the A2780 and 2780CPSlines. The 2780cps subline is also cross-resistant to these analogues in the relative order carboplatin > iproplatin > tetraplatin (most to least cross-resistant). Treatment of a highly cisplatin resistant cell line (2780CP70) with either melphalan or cisplatin was associated with a significant increase in [3H]thymidine incorporation into DNA in the presence of 10 mM hydroxyurea compared with the parent sensitive cell line which showed essentially no capacity to repair DNA damage by these drugs. A2780 and its cisplatin-resistant cell lines may thus be useful in studying drug resistance mechanisms, in screening new drugs for activity (especially against drug resistant tumors), and in formulating induction and salvage therapies for ovarian cancer.",
author = "Behrens, {Brent C.} and Hidetaka Masuda and Grotzinger, {Karen R.} and Jacqueline Whang-Peng and Louie, {Karen G.} and Turid Knutsen and Mckoy, {Wilma M.} and Young, {Robert C.}",
year = "1987",
month = "1",
day = "1",
language = "English",
volume = "47",
pages = "414--418",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - Characterization of a cis-Diamminedichloroplatinum(II)-resistant Human Ovarian Cancer Cell Line and its use in Evaluation of Platinum Analogues

AU - Behrens, Brent C.

AU - Masuda, Hidetaka

AU - Grotzinger, Karen R.

AU - Whang-Peng, Jacqueline

AU - Louie, Karen G.

AU - Knutsen, Turid

AU - Mckoy, Wilma M.

AU - Young, Robert C.

PY - 1987/1/1

Y1 - 1987/1/1

N2 - Human ovarian cancer cell lines with stable cisplatin resistance have been developed by chronic exposure of the parent cisplatin-sensitive A2780 line to increasing concentrations of cisplatin. 2780CP8. 2780CPS (CP8 refers to this cell line's growth in medium containing 8 μM cisplatin) has several clonal cytogenetic abnormalities but lacks homogeneously staining regions or double-minute chromosomes. It has a significantly greater monolayer growth rate, cloning efficiency in agarose, and total glutathione content compared to the A2780 line, but similar activities of several glutathione-dependent enzymes. The 2780cpsnsubline is 7.3-fold resistant to cisplatin compared to the A2780 line, as well as cross-resistant to irradiation and melphalan. It is not cross-resistant to Adriamycin, but this develops with increased cisplatin resistance (14-fold) obtained by further cisplatin exposure of 2780CPS. Of the cisplatin analogues tested which are of current clinical interest, carboplatin, iproplatin, and tetraplatin, only the latter is more cytotoxic than cisplatin in the A2780 and 2780CPSlines. The 2780cps subline is also cross-resistant to these analogues in the relative order carboplatin > iproplatin > tetraplatin (most to least cross-resistant). Treatment of a highly cisplatin resistant cell line (2780CP70) with either melphalan or cisplatin was associated with a significant increase in [3H]thymidine incorporation into DNA in the presence of 10 mM hydroxyurea compared with the parent sensitive cell line which showed essentially no capacity to repair DNA damage by these drugs. A2780 and its cisplatin-resistant cell lines may thus be useful in studying drug resistance mechanisms, in screening new drugs for activity (especially against drug resistant tumors), and in formulating induction and salvage therapies for ovarian cancer.

AB - Human ovarian cancer cell lines with stable cisplatin resistance have been developed by chronic exposure of the parent cisplatin-sensitive A2780 line to increasing concentrations of cisplatin. 2780CP8. 2780CPS (CP8 refers to this cell line's growth in medium containing 8 μM cisplatin) has several clonal cytogenetic abnormalities but lacks homogeneously staining regions or double-minute chromosomes. It has a significantly greater monolayer growth rate, cloning efficiency in agarose, and total glutathione content compared to the A2780 line, but similar activities of several glutathione-dependent enzymes. The 2780cpsnsubline is 7.3-fold resistant to cisplatin compared to the A2780 line, as well as cross-resistant to irradiation and melphalan. It is not cross-resistant to Adriamycin, but this develops with increased cisplatin resistance (14-fold) obtained by further cisplatin exposure of 2780CPS. Of the cisplatin analogues tested which are of current clinical interest, carboplatin, iproplatin, and tetraplatin, only the latter is more cytotoxic than cisplatin in the A2780 and 2780CPSlines. The 2780cps subline is also cross-resistant to these analogues in the relative order carboplatin > iproplatin > tetraplatin (most to least cross-resistant). Treatment of a highly cisplatin resistant cell line (2780CP70) with either melphalan or cisplatin was associated with a significant increase in [3H]thymidine incorporation into DNA in the presence of 10 mM hydroxyurea compared with the parent sensitive cell line which showed essentially no capacity to repair DNA damage by these drugs. A2780 and its cisplatin-resistant cell lines may thus be useful in studying drug resistance mechanisms, in screening new drugs for activity (especially against drug resistant tumors), and in formulating induction and salvage therapies for ovarian cancer.

UR - http://www.scopus.com/inward/record.url?scp=0023111825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023111825&partnerID=8YFLogxK

M3 - Article

C2 - 3539322

AN - SCOPUS:0023111825

VL - 47

SP - 414

EP - 418

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 2

ER -