Sequential study on the influence of adriamycin on cell proliferation and ultrastructure of cultured mammary tumor cells

Ahmad Safa, M. T. Tseng, R. J. Ballou

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Abstract

The time-dependent cytocidal and growth inhibitory effects of Adriamycin (ADM) on monolayer cultures of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor cells were analyzed. The inhibitory effect on cell proliferation was assessed by colony formation in soft agar. Growth inhibition and [3H]thymidine labeling indices clearly demonstrate a dose-dependent antimitotic and cytotoxic effect of the drug. At low concentration (10-9 -10-8 M), 90-100% of cells survived 24-hr exposure. At a higher concentration (10-5 M), 75-80% of cells survived after 8-hr exposure; by 72 hr only 20-30% of the cells remained. Autoradiographic examination of the pulse-labeled cultures demonstrated no change in the proportion of cells in S-phase during the first 4 hr of treatment. Subsequently DNA synthesis was completely abolished and remained inhibited for the duration of the experiment (72 hr). Clonogenic assay revealed a complete arrest of growth in cells exposed to 10-5 M ADM and greater than 60% inhibition of cell proliferation at 10-7 M. Ultrastructural changes were not observed in cells during the first 4 hr of treatment; however, after 8 hr most surviving cells exhibited alterations in nuclear chromatin. The surviving cells also showed mitochondrial degeneration, myelin body formation, and vacuolization of the endoplasmic reticulum. This study shows the potential usefulness of the primary culture system in drug evaluation. In addition, serial observation of the effects of ADM revealed a cell subpopulation of the primary culture with differential sensitivity to the drug.

Original languageEnglish (US)
Pages (from-to)276-283
Number of pages8
JournalProceedings of the Society for Experimental Biology and Medicine
Volume174
Issue number2
StatePublished - 1983
Externally publishedYes

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Cultured Tumor Cells
Cell proliferation
Doxorubicin
Tumors
Cells
Cell Proliferation
Breast Neoplasms
Pharmaceutical Preparations
Antimitotic Agents
9,10-Dimethyl-1,2-benzanthracene
Thymidine
Labeling
Agar
Chromatin
Monolayers
Assays
DNA
Growth
Drug Evaluation
Primary Cell Culture

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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abstract = "The time-dependent cytocidal and growth inhibitory effects of Adriamycin (ADM) on monolayer cultures of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor cells were analyzed. The inhibitory effect on cell proliferation was assessed by colony formation in soft agar. Growth inhibition and [3H]thymidine labeling indices clearly demonstrate a dose-dependent antimitotic and cytotoxic effect of the drug. At low concentration (10-9 -10-8 M), 90-100{\%} of cells survived 24-hr exposure. At a higher concentration (10-5 M), 75-80{\%} of cells survived after 8-hr exposure; by 72 hr only 20-30{\%} of the cells remained. Autoradiographic examination of the pulse-labeled cultures demonstrated no change in the proportion of cells in S-phase during the first 4 hr of treatment. Subsequently DNA synthesis was completely abolished and remained inhibited for the duration of the experiment (72 hr). Clonogenic assay revealed a complete arrest of growth in cells exposed to 10-5 M ADM and greater than 60{\%} inhibition of cell proliferation at 10-7 M. Ultrastructural changes were not observed in cells during the first 4 hr of treatment; however, after 8 hr most surviving cells exhibited alterations in nuclear chromatin. The surviving cells also showed mitochondrial degeneration, myelin body formation, and vacuolization of the endoplasmic reticulum. This study shows the potential usefulness of the primary culture system in drug evaluation. In addition, serial observation of the effects of ADM revealed a cell subpopulation of the primary culture with differential sensitivity to the drug.",
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