Induction of cytogenetic damage by modified steroidal derivatives of p-bis(2-chloroethyl)aminophenylacetic acid in human lymphocytes.
The effect of modified steroids, containing alkylating agents, on SCE rates and on cell kinetics in cultured human lymphocytes was studied. The homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE) was found to be the most effective in causing markedly increased SCE rates and cell division delays. The androsterone ester of p-bis(2-chloroethyl)aminophenylacetic acid (AE-CAPA) was found to be next in order of effectiveness with the lactone ester (LE-CAPA), chlorambucil ester 3 beta-hydroxy-13a-amino-13,17-seco-5a-androstan-17-oic-13,17-lactam (CBC-HAAL) and chlorambucil (CBC) following. p-Bis(2-chloroethyl)aminophenylacetic acid (CAPA) had only a small effect and 3 beta-hydroxy-13a-amino-13,17-seco-5a-androstan-17-oic-13,17-lactam (HAAL) had no effect at all. A correlation between potency for SCE induction, effectiveness in cell division delay and previously established antitumor activity of these drugs was observed.
D000731:Androstanes / Q000633:toxicity*; D001378:Azasteroids; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009588:Nitrogen Mustard Compounds / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000731:Androstanes; D001378:Azasteroids; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; C033499:3-(((4-(bis(2-chloroethyl)amino)phenyl)acetyl)oxy)-17a-aza-D-homoandrost-5-en-17-one