Detection of DNA strand breaks in Escherichia coli treated with platinum(IV) antitumor compounds.
DNA strand breaks were observed in bacteria treated with Pt(IV) but not Pt(II) antitumor compounds by two methods. First, compounds which cause DNA strand breaks produced an SOS induction signal which was detected by a rapid bacterial assay. In addition, the capacity of these compounds to cut DNA in vivo was directly measured by agarose gel electrophoresis of pBR322 DNA extracted from bacteria treated with these drugs. cis-Diamminetetrachloroplatinum(IV) (cis-DTP) and cis-dichloro-trans-dihydroxo-cis-bis(isopropylamine)-platinum(IV) (iproplatin) produced strand breaks in both assays while cis-diamminedichloroplatinum(II) (cisplatin) did not. These results indicate that Pt(IV) antitumor complexes may cause DNA damage in vivo which is not produced by Pt(II) compounds.
Defais
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Laboratoire de Pharmacologie et de Toxicologie Fondamentales du CNRS, Toulouse, France.
Germanier
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M
Johnson
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000032:analysis* / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010957:Plasmids; D001616:beta-Galactosidase / Q000096:biosynthesis
D000970:Antineoplastic Agents; D004277:DNA, Single-Stranded; D009944:Organoplatinum Compounds; C034697:transplatin; C041149:diamminetetrachloroplatinum(II); C023359:iproplatin; D001616:beta-Galactosidase; D002945:Cisplatin