| Autor: |
Scholz, Gabriele, Pohl, Ingeborg, Genschow, Elke, Klemm, Martina, Spielmann, Horst |
| Předmět: |
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| Zdroj: |
Cells Tissues Organs; 1999, Vol. 165 Issue 3/4, p203-211, 9p, 2 Diagrams, 3 Charts |
| Abstrakt: |
Blastocyst-derived pluripotent embryonic stem (ES) cells of the mouse can be induced to differentiate in culture into a variety of cell types, including cardiac muscle cells. The embryonic stem cell test that makes use of the differentiation of ES cells into cardiomyocytes in a standardized in vitro model was developed to offer an alternative method to comprehensive in vivo studies in reproductive toxicology about toxic effects of chemicals. ES cells of the mouse cell line D3 are investigated for their preserved capability to differentiate following drug exposure, and both ES cells and differentiated fibroblast cells of the mouse cell line 3T3 are comparatively analyzed for effects on viability. The following endpoints are used to classify the embryotoxic potential of chemicals into three classes of in vitro embryotoxicity (non-, weakly or strongly embryotoxic). These endpoints are: (1) the inhibition of differentiation of ES cells into cardiomyocytes after 10 days of treatment, and the decrease of viability (cytotoxicity) of (2) 3T3 cells and (3) ES cells after 10 days of treatment, determined by a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) test. 50% inhibition concentrations for differentiation (ID[sub 50] ) and cytotoxicity (IC[sub 50] D3 and IC[sub 50] 3T3) are calculated from concentration-response curves. Applying linear analysis of discriminance, a biostatistical prediction model (PM) was developed. This procedure identified three variables, the lg(IC[sub 50] D3), the lg(IC[sub 50] 3T3) and the relative distance between IC[sub 50] 3T3 and ID[sub 50] , that improved the separation of the three classes of embryotoxicity compared to the prediction model that was originally proposed after test development. Unlike the orginal PM, the improved PM incorporates as one variable the relative distance between IC[sub 50] 3T3 and ID[sub 50] , instead of the ratio ID[sub 50] /IC[sub 50] D3 that was used previously.Copyright © 1999 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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