Differential effect of D-penicillamine on the cell kinetic parameters of various normal and transformed cellular types.
The cell-growth-inhibitory and phase-specific effects of D-penicillamine on cell-cycle progression were investigated using cell-proliferation patterns, quantitative cell-cycle analysis by flow cytometry, and determination of the mitotic index and binucleate cell fraction of normal (rabbit articular chondrocytes, L 809, rabbit fibroblasts) and transformed (HeLa, L 929) cells. D-penicillamine treatment resulted in an inhibition of growth within a dose range of 5 x 10(-4) M to 7.5 x 10(-3) M. Examination of DNA by flow cytometric analysis revealed that rabbit articular chondrocytes were preferentially arrested in the G0/1 phase of the cell cycle, whereas the other cell lines were blocked in the G2 + M phase; the increase in the proportion of cells with G2 + M DNA content was partially due to an enhancement of binucleate cells, resulting in a cytokinesis perturbation for HeLa and L 929 cells. These results showed that D-penicillamine affects cell proliferation through different events according to cell type.
Friteau
L
L
Laboratoire de Pharmacologie Cellulaire de l'Ecole Pratique des Hautes Etudes, Institut Biomédical des Cordeliers, Paris, France.
Jaffray
P
P
Ronot
X
X
Adolphe
M
M
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008940:Mitotic Index / Q000187:drug effects; D010396:Penicillamine / Q000494:pharmacology*; D011817:Rabbits
D004247:DNA; D010396:Penicillamine