A comparison of the genotoxic effects of carboplatin and cisplatin in Escherichia coli.
cis-Diammine(1,1,-cyclobutanedicarboxylato)platinum(II) (carboplatin) is a second generation platinum anticancer agent with antineoplastic properties like that of its parent compound, cis-diamminedichloroplatinum(II) (cisplatin) but with substantially less deleterious side effects in treated patients with cisplatin. We compared their genotoxic effects in Escherichia coli and found carboplatin to be less cytotoxic (measured as loss of colony forming ability) that cisplatin in that equitoxic doses required greater than 60 time more carboplatin. However, solutions of carboplatin containing chloride ion became more cytotoxic to E. coli after a 24 h incubation period than similar freshly made solutions. Two platinum conversion products which were neither present in freshly made solutions nor in solutions lacking chloride were resolved by thin-layer chromatography (TLC). One of the conversion products migrated like cisplatin and its occurrence in carboplatin solutions was associated with cisplatin-like properties, enhanced cytotoxicity and ability to induce the SOS responses in E. coli. The SOS-inducing abilities were determined by induction of a sulA::lacZ fusion. Likewise, adducts formed in end-labeled oligonucleotides treated with carboplatin appeared identical to those caused by cisplatin when carboplatin was preincubated in chloride-containing solutions but not by carboplatin in freshly made solutions. It is likely that responses evoked by carboplatin in biological systems are partly due to activation of carboplatin by its conversion of cisplatin.
Overbeck
T L
TL
Department of Biological Sciences, Bowling Green State University, OH 43403, USA.
Knight
J M
JM
Beck
D J
DJ
D000970:Antineoplastic Agents / Q000633:toxicity*; D016190:Carboplatin / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004269:DNA, Bacterial / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D007364:Intercalating Agents; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009690:Nucleic Acid Conformation; D010957:Plasmids; D013014:SOS Response, Genetics / Q000187:drug effects; D014169:Transformation, Bacterial
D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D007364:Intercalating Agents; D009153:Mutagens; D016190:Carboplatin; D002945:Cisplatin