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) > cis (1) ∼ dien (0.7). DNA replication is reduced to 50% of the control when 1.8 × 10−4, 2.4 × 10−4 and 80 × 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.