TY - JOUR
T1 - Effects of Adriamycin on rat heart cells in culture
T2 - Increased accumulation and nucleoli fragmentation in cardiac muscle v. non-muscle cells
AU - Lampidis, Theodore J.
AU - Johnson, Lincoln V.
AU - Israel, Mervyn
N1 - Funding Information:
* This work was supported in part by research grants CA 24771 and CA 22427, and CA 19118 from the National Cancer Institute and by funds provided to T. J. Lampidis by Adria Laboratories Inc., Columbus, Ohio, U.S.A.
PY - 1981/10
Y1 - 1981/10
N2 - Primary cultures from neonatal rat hearts consist of morphologically distinguishable cardiac muscle and non-muscle cells. The relative fluorescence intensity and nucleolar effects of Adriamycin (ADR) have been studied in these different cell types by fluorescence and phase-contrast microscopy. In cultures exposed to ADR (10 μg/ml) for 30 min, or continuously for 24 h, the intensity of drug-specific fluorescence was significantly greater in the nuclei of muscle, as compared to non-muscle cells. Consistent with these differences in cytofluorescence, nucleolar fragmentation was observed in muscle cells 24 h after a 30-min exposure to ADR, whereas non-muscle cell nucleoli remained intact. With N-trifluoroacetyladriamycin-14-valerate (AD 32), a potent ADR analog, fluorescence was observed in the cytoplasm of both muscle and non-muscle cells; no difference in the intensity of fluorescence between these two cell types was detected. Based on these observations, we believe that drug-induced nucleolar fragmentation in cardiac muscle cells results from higher ADR levels than those achieved in non-muscle cells, and that these differences may have relevance with respect to anthracycline-induced cardiotoxicity in vivo.
AB - Primary cultures from neonatal rat hearts consist of morphologically distinguishable cardiac muscle and non-muscle cells. The relative fluorescence intensity and nucleolar effects of Adriamycin (ADR) have been studied in these different cell types by fluorescence and phase-contrast microscopy. In cultures exposed to ADR (10 μg/ml) for 30 min, or continuously for 24 h, the intensity of drug-specific fluorescence was significantly greater in the nuclei of muscle, as compared to non-muscle cells. Consistent with these differences in cytofluorescence, nucleolar fragmentation was observed in muscle cells 24 h after a 30-min exposure to ADR, whereas non-muscle cell nucleoli remained intact. With N-trifluoroacetyladriamycin-14-valerate (AD 32), a potent ADR analog, fluorescence was observed in the cytoplasm of both muscle and non-muscle cells; no difference in the intensity of fluorescence between these two cell types was detected. Based on these observations, we believe that drug-induced nucleolar fragmentation in cardiac muscle cells results from higher ADR levels than those achieved in non-muscle cells, and that these differences may have relevance with respect to anthracycline-induced cardiotoxicity in vivo.
KW - AD 32
KW - Adriamycin
KW - Cardiotoxicity
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U2 - 10.1016/0022-2828(81)90290-X
DO - 10.1016/0022-2828(81)90290-X
M3 - Article
C2 - 7310895
AN - SCOPUS:0019801451
VL - 13
SP - 913
EP - 924
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 10
ER -