Doxorubicin-induced ultrastructural and growth changes in primary cultures of 7,12-dimethylbenz[a]anthracene-induced mammary tumors

Ahmad Safa, M. T. Tseng

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

For the determination of their response to doxorubicin (Dx) (adriamycin), monodispersed mammary tumor cells (from female outbred Sprague-Dawley rats) were maintained as monolayer primary culture. Dose-response curves and [3H]thymidine labeling indices showed the antimitotic and cytocidal effects of the drug varied in a dose-dependent fashion. Dose-response curves revealed that the median lethal dose concentration was 10-4 M. A 24-hour treatment at concentrations of 10-4 to 10-5 M completely arrested DNA synthesis of the tumor cells. Surviving cells exhibited chromatin abnormalities, accumulation of cytoplasmic myelin bodies, vacuolization of endoplasmic reticulum, and increased density of mitochondrial matrix. This study showed 1) 7,12-dimethylbenz[a]anthracene-induced mammary tumor cells were highly sensitive to Dx; 2) Dx induced specific ultrastructural effects on the nuclei, mitochondria, and membranes of the cells; and 3) the in vitro response of the primary culture may be useful for prediction of the response of the source tumor to chemotherapy.

Original languageEnglish (US)
Pages (from-to)535-540
Number of pages6
JournalJournal of the National Cancer Institute
Volume70
Issue number3
StatePublished - 1983
Externally publishedYes

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Doxorubicin
Breast Neoplasms
Growth
Antimitotic Agents
Myelin Sheath
Endoplasmic Reticulum
Thymidine
Chromatin
Sprague Dawley Rats
Neoplasms
Mitochondria
Cell Membrane
Drug Therapy
anthracene
DNA
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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abstract = "For the determination of their response to doxorubicin (Dx) (adriamycin), monodispersed mammary tumor cells (from female outbred Sprague-Dawley rats) were maintained as monolayer primary culture. Dose-response curves and [3H]thymidine labeling indices showed the antimitotic and cytocidal effects of the drug varied in a dose-dependent fashion. Dose-response curves revealed that the median lethal dose concentration was 10-4 M. A 24-hour treatment at concentrations of 10-4 to 10-5 M completely arrested DNA synthesis of the tumor cells. Surviving cells exhibited chromatin abnormalities, accumulation of cytoplasmic myelin bodies, vacuolization of endoplasmic reticulum, and increased density of mitochondrial matrix. This study showed 1) 7,12-dimethylbenz[a]anthracene-induced mammary tumor cells were highly sensitive to Dx; 2) Dx induced specific ultrastructural effects on the nuclei, mitochondria, and membranes of the cells; and 3) the in vitro response of the primary culture may be useful for prediction of the response of the source tumor to chemotherapy.",
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