Induction of chromosomal aberrations in human lymphocytes by the antitumour alkylating agent homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenoxy acetic acid, in vitro

The clastogenic activity of the antineoplastic alkylating agent 3β-hydroxy-13-amino-13,17-seco-5-androstan-17-oic- 13,17-lactam-p-bis (2-chloroethyl) aminophenoxy acetic acid (NSC 294859) and its congeners was studied in human lymphocyte cultures in vitro. Cells were exposed to several concentrations of the drugs for 24 h. It was found that NSC 294859 reduces the mitotic index and causes chromosome- as well as chromatid-type aberrations in a dose-dependent way. From its congeners, the alkylating agent (p-bis (2-chloroethyl) aminophenoxy acetic acid) induces the same phenomena but to a lesser extent, while the modified steroid (3β-hydroxy-13-amino-13,17-seco-5-androstan-17-oic-13,17-lactam) causes cytogenetic damages at the control level. These results favour the assumption that the antitumor activity of NSC 294859 is mainly based on its cytogenetic effects.