During intermittent alkylating drug therapy the in vitro myeloma cell thymidine-3 H-labeling index increases progressively after each treatment course to values as high as 45%. Elevated tumor cell-labeling indices are observed in both responding and nonresponding myeloma patients after cell cycle-nonSpecific therapy. In order to determine the mechanism underlying the increased labeling index in treated myeloma patients, we performed autoradiographic studies in which bone marrow cells were incubated with cytosine arabinoside (105 M) or hydroxyurea (103M) before exposure to thymidine-3 H. In all five patients studied, incubation of the myeloma cells with either of the S-phase-Specific agents resulted in marked inhibition of thymidine-3H uptake. These observations indicate that scheduled (prereplicative) and not repair DNA synthesis is the basic mechanism underlying the high labeling indices. The concentrations of cytosine arabinoside and hydroxyurea, which block DNA synthesis by myeloma cells in vitro, are in the range attainable in vivo. Cell cycle-Specific antitumor agents could potentially be effective in myeloma patients when the tumor cell-labeling index is elevated after cell cycle-nonSpecific therapy.
|Original language||English (US)|
|Number of pages||4|
|State||Published - Nov 1974|
ASJC Scopus subject areas
- Cancer Research