EVALUATION OF IN VITRO TOXICITY OF 32 MEIC COMPOUNDS TOWARDS HUMAN NATURAL KILLER CELL FUNCTION

YOSHIO KOBAYASHI1, TAKASHI YAMASHIRO1, NAOKO WATANABE1 and TADAO OHNO2
1Laboratory of Molecular Immunology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274, Japan; 2Riken Cell Bank, Institute of Physical and Chemical Research (RIKEN), 3-3-1 Koyedai, Tsukuba, Ibaraki 305, Japan 1Department of Clinical Pharmacy, Kyoritsu College of Pharmacy, 1-5-30, Shibakoen, Minato-ku, Tokyo 105 Japan; 2Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 9-1, Shirokane 5 Chome, Minato-ku, Tokyo 108 Japan; 3Department of Clinical Pharmacokinetics, Division of Pharmaceutical Sciences, Graduate School, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812 Japan

Original:AATEX 4(2):63-72

Abstract
To develop a method of determining the immunotoxicity of chemicals, the effects of MEIC compounds on the cytotoxic function of a human natural killer (NK) cell-rich population cultured in vitro were examined. Twenty of 32 MEIC compounds showed apparent inhibition of NK cell mediated cytotoxic activity. The concentrations causing 50% inhibition (IC50 values) were highly correlated (r=0.86) with previously reported effective doses for inhibiting human squamous carcinoma cell growth by 50% of the level in control cells (ED50 values). In general, inhibition of NK cell-mediated cytotoxic activity was more profound than inhibition of cell growth. Some compounds preferentially affected the NK cell function but not target cell susceptibility, as evidenced by the effect of brief exposure of these compounds on effecter cells and target cells. Thus, a NK cell-mediated cytotoxic assay with a cultured human NK cell-rich population may be a sensitive method for clarifying important aspects of the immunotoxicity of chemicals in vitro.


Key words: doxorubicin, chronopharmac


return