Enhancement of Mitotic Activity by Fluorene Derivatives

Abstract

Twelve fluorene derivatives representing simple modifications of the basic fluorene molecule have been studied for their effect on two unicellular Flagellata: Polytoma uvella, a chlorophyll-free, heterotrophic Volvocales, and Astasia longa, a heterotrophic, euglenoid flagellate. The experiments were evaluated by nuclear counts after 21 hours (Polytoma) and 48 hours (Astasia) of incubation in the presence and absence of the fluorene derivative. Owing to the high sensitivity of the two assay systems, a wide dose range, from 10⁻⁵ g/ml. to 10⁻¹¹ g/ml. could be studied. The response of the organisms consisted in an altered division rate. The dose-response curves were typical for each agent. Fluorene was inactive in both test systems; aminofluorene was active. Acetylation of aminofluorene, particularly in the 2-position, added biological activity to the aminofluorene molecule. Diacetylation strengthened this effect. Hydroxylation of fluorene was more effective in the 1- or 3-position than in the 2-position. The most active compound assayed in this series was 3-OH-2-FAA [N-(3-hydroxy)-2-fluorenylacetamide]; 10⁻¹⁰ g/ml. still induced 20 percent enhancement of the mitotic rate. Deviation of ±10 percent from the baseline (untreated culture) can be considered significant under the standard conditions described. The usefulness of protozoa for certain aspects of cancer research is discussed. Similarities of the physiological characteristics of the protozoan cell and the mammalian cell are pointed out.