Enhanced cytogenetic and antineoplastic effects by the combined action of two esteric steroidal derivatives of nitrogen mustards.
The authors studied the effect of two modified steroids containing different proportions (%) of alkylating agents alone or in combination on sister chromatid exchange (SCE) rates and on human lymphocyte proliferation kinetics. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The two chemicals in mixtures enhance SCE induction and antitumor activity in a synergistic manner. The homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenyl acetic acid was found to be more effective than the homo-aza-steroidal ester of o-bis(2-chloroethyl)aminobenzoic acid in causing cytogenetic damage and antineoplastic activity. A correlation was observed between the magnitude of the SCE response and the depression of the cell proliferation index. The order of the antitumor effectiveness of the five different treatments tested coincided with the order of the cytogenetic effects they induced.
Papageorgiou
A
A
Laboratory of Experimental Chemotherapy, Theagenion Anticancer Institute, Thessaloniki, Greece.
Nikolaropoulos
S S
SS
Arsenou
E S
ES
Karaberis
E
E
Mourelatos
D
D
Kotsis
A
A
Chryssogelou
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001378:Azasteroids / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007939:Leukemia L1210; D007941:Leukemia P388; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001378:Azasteroids; D009588:Nitrogen Mustard Compounds; C117134:3-hydroxy-13-amino-13,17-seco-5alpha-androstan-17-oic-13,17-lactam 2-N,N-bis(2-chloroethyl)aminobenzoate; C017888:NSC 290205