Nuclear DNA binding and inhibition of growth of HeLa cells in culture were determined after 24 h incubation with the ruthenium anticancer agents cis-[Cl2(NH3)4Ru]Cl (CCR) and (ImH)trans-[(Im)2Cl4Ru] (ICR) as a function of [Ru], Po2, and added transferrin. Consistent with the “activation-by-reduction” hypothesis, cytotoxicity and DNA binding for both complexes increased under reduced oxygen conditions. Consistent with the “transferrin- transport” hypothesis, inhibition of cell growth also increased with added transferrin for both complexes. Despite their differences in charge, reduction potentials and substitution rates, both complexes behaved remarkably similarly indicating a common mechanism of action for both. Under atmospheric Conditions (Po2 = 159 torr), CCR inhibited HeLa cell growth with IC50 = 3.5 μM, while that for ICR was 2.0 μM. The binding of both complexes to DNA (RuDNA/PDNA) correlated with toxicity and was approximately linear in the concentration of the ruthenium complex in the culture medium, [Ru]. For both complexes, IC50 values decrease and DNA binding increases with decreasing log(Po2). In general, DNA binding at all oxygen pressures for both complexes is in the range of one Ru per 1000-2000 DNA base pairs at [Ru] = IC50.

Complexing of 3,4-benzpyrene (BP) with a series of nucleosides, 5 '-nucleotides, native and denatured deoxyribonucleic acid (DNA), calf thymus nucleohistone, synthetic polyribonucleotides, and yeast ribonucleic acid (RNA) has been investigated using radiochemical assay methods. Physical binding to the polynucleotides and nucleohistone has been demonstrated by sucrose gradient electrophoresis and ultracentrifugation.

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