DNA-protein crosslinks as a biomarker of cis-platinum activity in cancer patients

We have developed a new method to assess the amount of DNA-protein crosslinks (DNA-PC) in peripheral lymphocytes, based on the selective precipitation of the DNA crosslinked to proteins. We assessed the amount of DNA-PC in peripheral lymphocytes of 18 cancer patients who underwent chemotherapy with cis-platinum for the first time. Since the chemotherapy was administered over a two-day period, blood samples were drawn at baseline (before starting the therapy), 4 h after the infusion of the first dose of cis-platinum, the next day (24 h after the first dose, and immediately before the infusion of the second dose), and 2 days later (48 h after the first dose). The mean change of DNA-PC 4 h after therapy was 0.8+/-0.8% (p=0.006), 0.5+/-0.6% after 1 day (p=0.007), and 0.1+/-0.5% after two days (ns). The correlation between DNA-PC changes and cumulative dose of cis-platinum was -0.22 at 4 h, -0.19 after 1 day, and -0.68 at 2 days (p=0.005). The crosslinking effect of cis-platinum seems to vary among individuals and with dose; the DNA-PC may be used to define sub-populations of patients with various degree of sensitivity to the pharmacologic action of this chemotherapeutic agent, and thus to adjust the dosage on an individual basis.