Comparison of the induction of SOS repair in Escherichia coli PQ37 and PQ243 by antineoplastic agents.
Six alkylating antineoplastic drugs (Cyclophosphamide, Chlorambacil, Busulfan, Melphalan. Streptozotocin and Lomustine) and two reference compounds (methyl methanesulphonate and N-methyl-N'-nitro-N-nitrosoguanidine) were investigated in the SOS Chromotest using the Escherichia coli strain PQ37 (wilde-type) and derived strain (PQ243), which carries the same markers as PQ37 and additionally tagA alkA. As a measure of the SOS induced activity induction factors of sflA::lacZ expression were determined. The strain PQ243 was more sensitive towards all compounds inducing SOS DNA repair then the strain PQ37 Cyclophosphamide was detected as negative in the strain PQ243 in the presence of an exogenous metabolic activation system. Lomustine was inactive both in the mutant strain and in the wild-type strain in the presence of S9 mix fraction as well as in the absence of it. Melphalan and Busulfan (without or with S9 mix) were shown to be positive exclusively in the strain PQ243. Based on these results, we discuss the usefulness of the strain PQ243 in the monitoring of the genotoxicity of drugs and in the genetic analysis of their mode of action.
Marczewska
J
J
Drug Institute, Warsaw, Poland.
Koziorowska
J
J
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002066:Busulfan / Q000494:pharmacology; D002699:Chlorambucil / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000235:genetics; D007763:Lac Operon / Q000187:drug effects / Q000235:genetics; D008130:Lomustine / Q000494:pharmacology; D008558:Melphalan / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009152:Mutagenicity Tests; D013014:SOS Response, Genetics / Q000187:drug effects*; D013311:Streptozocin / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D013311:Streptozocin; D008130:Lomustine; D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan