During intermittent alkylating drug therapy the in vitro myeloma cell thymidine 3H 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, autoradiographic studies were performed, in which bone marrow cells were incubated with cytosine arabinoside (10-5 M) or hydroxyurea (10-3 M) before exposure to [3H] thymidine. In all five patients studied, incubation of the myeloma cells with either of the S phase specific agents resulted in marked inhibition of [3H] thymidine 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|
|Publication status||Published - 1974|
ASJC Scopus subject areas
- Cancer Research