cis-Pt(NH3)2Cl2 and trans-Pt(NH3)2Cl2 inhibit DNA synthesis in cultured L1210 leukemia cells.
A comparison of the inhibition of DNA synthesis by the two geometrical bidentate isomers cis- and trans-Pt(NH3)2Cl2 and by the monodentate [Pt(dien)Cl]Cl in a model used for screening potential antitumor compounds, the L1210 leukemia cells, is presented. The efficacy of penetration after a 2 hours Pt treatment is in the order trans (8) greater than cis (1) approximately dien (0.7). DNA replication is reduced to 50% of the control when 1.8 X 10(-4), 2.4 X 10(-4) and 80 X 10(-4) Pt atoms were bound per nucleotide for cis, trans and dien derivatives, respectively. If we admit that DNA is the pharmacological target of Pt antitumor compounds, these results suggest that a quantitative inhibition of DNA synthesis is certainly not correlated with antitumor activity.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D002945:Cisplatin