EFFECTS OF HYPOXIA, PH, AND GROWTH STAGE ON CELL KILLING IN CHINESE-HAMSTER V79 CELLS-INVITRO BY ACTIVATED CYCLOPHOSPHAMIDE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (8) , 3454-3459
Abstract
Several factors which influence the sensitivity of Chinese hamster V79 [lung fibroblast] cells to cyclophosphamide (CY) [an antineoplastic agent] were studied in vitro in both suspension and monolayer cultures. Activated CY was obtained from the blood of mice 15-30 min after i.p. injection of CY (400 mg/kg). At pH 7.4, hypoxia rendered the cells more sensitive to activated CY. At lower values of pH (6.6 and 7.0), there was no difference between the sensitivities of oxic and hypoxic cells, although cells in both conditions were more sensitive to CY than at pH 7.4. Drug sensitivity was markedly affected by the stage of cell growth. Monolayer cultures were most sensitive to CY within a few hours of plating. Cultures then rapidly became less sensitive, with maximum resistance occurring between 24 and 48 h after plating, while the cells were still exhibiting rapid exponential growth. This development of resistance paralleled the formation of small colonies (2-4 cells), implying that intercellular contact may confer resistance to killing by activated CY.