Polyclonal antibodies to quantitate cis-diamminedichloroplatinum(II)--DNA adducts in cancer patients and animal models.
cis-Diamminedichloroplatinum (II) (cis-DDP), the antitumor drug, is cytotoxic in vitro primarily by binding to DNA and disrupting its normal functions. We have studied cis-DDP modification of DNA in nucleated peripheral blood cells (buffy coat cells) of testicular and ovarian cancer patients receiving cis-DDP chemotherapy, and of untreated controls. Using a highly sensitive enzyme-linked immunosorbent assay (ELISA) with an antiserum specific for the bidentate intrastrand N7-deoxyguanosine adduct, blood cell DNA was assayed at multiple times during courses of cis-DDP treatment. A total of 138 samples were analyzed from 54 individuals. Of these, all samples from 18 untreated controls were negative, while 44 out of 120 samples from cis-DDP patients were positive. Testicular and ovarian cancer patients receiving chemotherapy on the first course, and given cis-DDP in 21- or 28-day cycles (five days of drug infusion followed by two or three drug-free weeks) accumulated cis-DDP-DNA adducts in blood cell DNA as a function of dose. Patients receiving their first course of cis-DDP on 56-day cycles and those given high doses of this drug after failing other chemotherapy showed much slower adduct accumulation than patients receiving their first course on 21- or 28-day cycles. Adduct accumulation, in positive patients, occurred both as a function of total cumulative dose and with increasing cycle number, suggesting that adduct removal took at least a month in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex; D002945:Cisplatin / Q000032:analysis / Q000378:metabolism*; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007668:Kidney / Q000032:analysis; D009369:Neoplasms / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats
D000906:Antibodies; D000936:Antigen-Antibody Complex; D004247:DNA; D002945:Cisplatin