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increased lifespan over controls in the treatment of L1210 N.A.Demopoulos leukemia in mice and a 150% increased lifespan in the treatment of P388 leukemia (Wampler and Catsoulacos, 1977).Division of Genetics, Cell and Developmental Biology, Department of Moreover, ASE has given good activity against B 16 melanoma Biology, University of Patras, 26500 Patras, Greece in C 57 b 1 mice and T 8 Guerrin tumors in rats (Catsoulacos and 3β-Hydroxy-13α-amino-13,17-seco-5α-androstan-17- Wampler, 1982). In addition, ASE alone or in combination oic-13,17-lactam-p-bis(2-chloroethyl)amino phenylacetate with a different modified steroid, the homo-aza-steroidal ester (ASE) is a homo-aza-steroidal ester of p-bis(2-chloroethyl)of o-bis(2-chloroethyl)aminobenzoic acid, proved to exert amino phenyl acetic acid and has been shown to display enhanced antitumor activity in a synergistic manner antineoplastic, mutagenic and genotoxic activity. In the (Papageorgiou et al., 1999). It is noteworthy that although present study an effort has been made to evaluate the ASE exerts about the same antineoplastic activity as ability of ASE to induce micronuclei (MN) in human chlorambucil, it is less toxic with a more prolonged action lymphocytes treated in vitro using the cytokinesis-block (Stevenson and Patel, 1973; Catsoulacos et al., 1978). assay. Lympocytes were treated with different concentraAdditionally, ASE has shown mutagenic properties. It was tions of ASE (0.1, 0.25, 0.5, 1, 2.5, 5, 10 and 20 µg/ml) at found to be positive in strains TA1535 and TA100 as well as two different cell culture times, 21 and 41 h after culture in strain TA102 with and without metabolic activation in the initiation. ASE treatment lasted until cell harvest, for Salmonella/microsome system (Athanasiou and Arzimanoglou, 51 and 31 h, respectively. Two types of cultures were used, 1986). The compound has also been shown to induce sister whole blood and isolated lymphocyte cultures. The content chromatid exchange in human lymphocytes (Mourelatos et al., of induced MN was identified by FISH analysis, using an 1987) as well as in CHO cells (Athanasiou et al., 1983). ASE α-satellite DNA probe, in binucleate cells. Our results was also determined to decrease protein synthesis rate in suggest that ASE is capable of increasing MN frequencies ovaries of Drosophila melanogaster (Stephanou et al., 1991). in human lymphocytes under both culture conditions. ThisFinally, ASE was identified as displaying genotoxic, cytostatic increase is related to the concentration in a linear doseand antineoplastic properties (Nikolaropoulos et al., 1997). dependent manner and is also dependent on the duration Human lymphocytes cultured in vitro have been widely of treatment. FISH analysis has shown that the induced used as an appropriate system to identify the genetic activity MN resulted mainly from breakage events. Additionally, of various chemical compounds. They are a more or less a weak aneugenic effect was found at the higher conhomogeneous cell population, being all in the G 0 phase, an...