Deuterium oxide (heavy water) arrests the cell cycle of PtK2 cells during interphase.
Deuterium oxide (D2O, heavy water) exerts an antiproliferative effect on a variety of cells in vitro and on some organisms. This effect is mainly ascribed to a tubulin-mediated antimitotic action. We evaluated the morphology, the mitotic activity, and the dynamics of the cell cycle of PtK2 cells grown in vitro in the presence of 75% D2O for up to eight weeks by microspectrophotometric DNA measurements as well as flow cytometric analysis and a determination of mitotic indices. Substitution of heavy water for water in the culture medium initially increased the mitotic index by a (pro-) metaphase block but after 2 to 3 days of incubation no mitotic figures were seen. Analysis of cells grown for 6 days in medium containing 75% D2O revealed accumulation of cells in S/G2-phase. Extended treatment stabilized the high level of cells in this specific phase, when compared to normal growing cells. Cells grown for 1 to 6 weeks in the presence of D2O remained non-proliferating, nevertheless, they were able to divide again after recovery in non-deuterated medium. The time needed for resumption of the mitotic activity was proportional to the duration of deuterium oxide exposure. Cells incubated for 8 weeks in 75% D2O did not recommence mitotic activity. Light and electron microscopic examination revealed characteristic morphological changes of size and ciliation in PtK2 cells subjected to prolonged deuteration.(ABSTRACT TRUNCATED AT 250 WORDS)
Schroeter
D
D
Institute of Cell and Tumor Biology, German Cancer Research Center, Heidelberg.
Lamprecht
J
J
Eckhardt
R
R
Futterman
G
G
Paweletz
N
N
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004247:DNA / Q000032:analysis; D003903:Deuterium / Q000494:pharmacology*; D017666:Deuterium Oxide; D005434:Flow Cytometry; D007399:Interphase; D007614:Macropodidae; D015591:Microspectrophotometry; D014867:Water / Q000494:pharmacology*
D014867:Water; D004247:DNA; D003903:Deuterium; D017666:Deuterium Oxide