Studies of
platinum drug-
DNA adduct formation in tissues of
cancer patients have involved both atomic absorbance spectroscopy (AAS), which measures total
DNA-bound
platinum, and anti-
cisplatin-
DNA enzyme-linked
immunosorbent assay (ELISA), which detects a fraction of the AAS-measurable adduct. These studies were designed to explore mechanisms of
drug-
DNA interactions, to make correlations with clinical outcome, and possibly to validate
DNA adduct measurements for use in occupational and environmental biomonitoring. The results, determined by both ELISA and AAS, demonstrate that
cisplatin and its analog
carboplatin bind to
DNA in many human organs, including kidney, brain, peripheral nerve, and bone marrow, which are sites for
drug toxicity.
Platinum was also observed bound to ovarian
tumor DNA. The adducts were highly persistent, being measurable in tissues obtained at autopsy up to 15 months after the last administration of
platinum chemotherapy. A comparison of blood cell
DNA adduct levels, determined by ELISA, and the clinical response of 139 patients with ovarian, testicular, colon, or
breast cancer demonstrated a strong correlation between failure to form
DNA adducts and failure of
therapy. Conversely, patients who formed high levels of
DNA adduct were most likely to respond favorably. A similar correlation was not observed for adducts determined by AAS; that is, the average total
DNA-bound
platinum levels were the same for patients who did not respond to
therapy and for patients who had any kind of response. Thus, in this study, human blood cell
DNA adducts measured by ELISA correlate with
tumor remission, while those measured by AAS do not.