title: Dose- and pH-Dependent effects of chloroquine on Tetrahymena.
abstract: The effects of chloroquine (CQ), the antimalarial drug, were studied on Tetrahymena grown at pH 6.2, 6.8 (standard pH), 7.0, 7.4, and 8.0. At these pH values, the highest tolerated concentrations of the drug were 50, 5, 2.5, 0.5, and 0.05 mM, respectively; in these concentrations, cell proliferation continued at a decreased rate, but ceased at increased concentration and pH. At a given pH value, CQ had a dose-dependent effect on the initial lag period and on the cell generation time; the rate of endocytosis was increased about 25%, apart from in the highest concentration. All CQ-treated cells contained small refractive granules; their number remained constant in proliferating cells (fusion with food vacuoles), but increased in growth-inhibited cells. The fine structure of proliferating and inhibited cells is described. In the 1000-fold difference in the tolerated concentration of CQ in media ranging from pH 6.2 to 8.0, the calculated (pKs: 8.1 and 10.1) absolute amount of the neutral species of CQ is constant, whereas the amounts of the di- and mono-cation vary by a factor of 1764 and 27, respectively. Hence the toxicity of the drug to Tetrahymena seems directly related to the amount of the neutral species of CQ.
authors.affiliation: Institute of Cell Biology and Anatomy, The Zoological Institutes, University of Copenhagen, Denmark.
authors.forename: J R
authors.initials: JR
authors.lastname: Nilsson