DNA adducts of cisplatin and carboplatin in tissues of cancer patients.
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.
Poirier
M C
MC
National Cancer Institute, Bethesda, MD.
Egorin
M J
MJ
Fichtinger-Schepman
A M
AM
Yuspa
S H
SH
Reed
E
E
D000970:Antineoplastic Agents / Q000378:metabolism*; D016190:Carboplatin; D002945:Cisplatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000378:metabolism*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D004247:DNA; D016190:Carboplatin; D002945:Cisplatin