An
enzyme-linked
immunosorbent assay (ELISA) has been developed with an antiserum elicited against
cisplatin-modified
DNA and used to quantify the intrastrand bidentate
d(GpG)- and
d(ApG)-diammineplatinum adducts in
DNA samples prepared from nucleated blood cells and tissues of
cancer patients receiving
cisplatin or
carboplatin chemotherapy. In nucleated blood cell
DNA, adducts accumulated with increasing dose administered over a period of months, and a correlation was observed between the ability of a patient to form high levels of adduct and the frequency of tumour remission. Thus, many patients who did not form adducts also did not respond to
therapy. Adduct distribution was shown to be widespread in many human tissues, and similar quantities of adducts were formed in peripheral blood cell
DNA and tumour tissue. In addition, evidence suggests that residues of persistent adducts remain in many tissues weeks and even months
after treatment. All of the above observations were obtained with the
cisplatin-
DNA ELISA; however, in comparison with other published data, the adduct levels reported are low. It now appears certain that the
cisplatin-
DNA ELISA results in an underestimation of adduct values in
biological samples, since some human samples have been assayed by both this and two other procedures--the G-Pt-GMP ELISA and atomic absorbance spectroscopy. Values obtained with the two other procedures compare well with each other, but those obtained with the
cisplatin-
DNA ELISA for three human samples are 10-300-fold lower. The factors that result in this discrepancy are still under investigation.