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PubMed · 7209999

Platinum compounds with anti-tumour activity.

A C Plooy·P H Lohman
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Abstract

Ten platinum (Pt) coordination complexes with different ligands, comprising both Pt(II) and Pt(IV) complexes of which the cis-compounds all possessed at least some anti-tumour activity and the trans-compounds were inactive, were tested as to their effect on cell survival and the induction and repair of DNA damage in cultured Chinese hamster cells (CHO). The tests used were the determination of cytotoxicity, inhibition of the semi-conservative DNA replication, induction of damage in DNA and mutagenicity. The Pt-compounds could be divided in 3 groups on the basis of their cytotoxicity. The compounds with high cytotoxicity were also active anti-tumour drugs, but a clear correlation between cytotoxicity and anti-tumour activity was not observed. All compounds inhibited semi-conservative DNA synthesis and induced DNA repair replication. No induction of DNA single strand breaks and DNA cross-links was detected. However, the occurrence of alkali labile sites in the DNA of treated CHO cells demonstrated the induction of unidentified DNA base damages. The 4 compounds tested so far, 2 cis- and 2 trans-Pt complexes, induced mutations in CHO cells, leading to resistance to 6-thioguanine; the cis-compounds were more mutagenic than the trans-compounds.

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AlkaliesAnimalsAntineoplastic AgentsCricetinaeDNADNA ReplicationIn Vitro TechniquesPlatinumStructure-Activity RelationshipJournal ArticleResearch Support, Non-U.S. Gov't

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A C Plooy, P H Lohman. 1980. Platinum compounds with anti-tumour activity.. https://doi.org/10.1016/0300-483x(80)90090-6

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