Polyclonal antibodies to quantitate cis-diamminedichloroplatinum(II)--DNA adducts in cancer patients and animal models. 1985

M C Poirier, and E Reed, and L A Zwelling, and R F Ozols, and C L Litterst, and S H Yuspa

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)

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D000936 Antigen-Antibody Complex The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES. Immune Complex,Antigen-Antibody Complexes,Immune Complexes,Antigen Antibody Complex,Antigen Antibody Complexes,Complex, Antigen-Antibody,Complex, Immune,Complexes, Antigen-Antibody,Complexes, Immune

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