Mutagenesis, Vol. 15, No. 3, 215-221,
May 2000
© 2000 UK Environmental Mutagen Society/Oxford University Press
Evaluation and characterization of micronuclei induced by the antitumour agent ASE [3ß-hydroxy-13
-amino-13,17-seco-5-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl)amino phenylacetate] in human lymphocyte cultures
Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, 26500 Patras, Greece
3ß - Hydroxy - 13
- amino - 13, 17 - seco - 5 - androstan - 17 -oic-13,17-lactam-p-bis(2-chloroethyl)amino phenylacetate (ASE) is a homo-aza-steroidal ester of p-bis(2-chloroethyl) amino phenyl acetic acid and has been shown to display antineoplastic, mutagenic and genotoxic activity. In the present study an effort has been made to evaluate the ability of ASE to induce micronuclei (MN) in human lymphocytes treated in vitro using the cytokinesis-block assay. Lympocytes were treated with different concentrations of ASE (0.1, 0.25, 0.5, 1, 2.5, 5, 10 and 20 µg/ml) at two different cell culture times, 21 and 41 h after culture initiation. ASE treatment lasted until cell harvest, for 51 and 31 h, respectively. Two types of cultures were used, whole blood and isolated lymphocyte cultures. The content of induced MN was identified by FISH analysis, using an -satellite DNA probe, in binucleate cells. Our results suggest that ASE is capable of increasing MN frequencies in human lymphocytes under both culture conditions. This increase is related to the concentration in a linear dose-dependent manner and is also dependent on the duration of treatment. FISH analysis has shown that the induced MN resulted mainly from breakage events. Additionally, a weak aneugenic effect was found at the higher concentrations in whole blood cultures as well as in isolated lymphocyte cultures. Cytotoxic effects of ASE were observed under both cell culture conditions with a linear dose-dependent relationship according to CBPI evaluation and were more pronounced in isolated lymphocyte cultures.
* To whom correspondence should be addressed. Tel: +30 61 997 168; Fax: +30 61 997 185; Email: geosteph{at}biology.upatras.gr
This paper is dedicated to the memory of P. Catsoulacos, late Professor of Pharmaceutical Sciences at the University of Patras
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