A topographic study on the distribution of cisplatin in xenografted tumors on nude mice

The intratumoral distribution of cisplatin was studied in terms of platinum concentrations in tissue pieces and immunohistochemically detected cisplatin-DNA adducts in xenografted tumors on nude mice. Heterogeneities in drug distribution were calculated as standard deviations and coefficients of variation. A three-dimensional image of adduct distribution was produced which showed regions with low adduct levels to be topographically connected also in three dimensions. A model was presented for investigating the potential influence of vascularization and cell proliferation on intratumoral adduct distribution by using different immunohistochemical stainings of parallel tissue sections. A weak but significant correlation was found between cisplatin-DNA adducts and proliferation, which might indicate that the drug uptake and adduct formation is increased in proliferating cells.