Characterization of the DNA damage recognized by the antiserum elicited against <i>cis</i>-diamminedichloroplatinum (II)-modified DNA

Reed, Eddie; Gupta-Burt, Shalina; Litterst, Charles L.; Poirier, Miriam C.

doi:10.1093/carcin/11.12.2117

Cited by 23 publications

(15 citation statements)

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“…Further, tumor and bone marrow tissue obtained at autopsy from patients who had been treated with platinum compounds have similar levels of platinum-DNA adducts (6,9,10). These studies have received some criticism because of the use of polyclonal antisera to detect adducts in an enzyme-linked immunosorbent assay (ELISA), the results of which do not correlate well with platinum-DNA damage levels measued by atomic absorbance spectrometry (AAS) (11).…”

Section: Introductionmentioning

confidence: 99%

Cisplatin-DNA Damage and Repair in Peripheral Blood Leukocytes in Vivo and in Vitro

Dabholkar¹,

Bradshaw²,

Parker³

et al. 1992

Environmental Health Perspectives

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We have extended our studies on the relationship between cisplatin/carboplatin-induced DNA damage in readily accessible tissue(s) and clinical response to therapy. Such an approach may assist in the study ofcancer drug resistance and in establishing parameters for assessing human populations for sensitivity to DNA damaging agents in the environment. Platinum-DNA adduct levels were measured by atomic absorbance spectrometry. DNA repair capacity was assessed in human T-lymphocytes by the ability to repair cisplatin lesions in cellular DNA or in transfected plasmid DNA. In a "blinded" study of 21 patients receiving combination cisplatin/carboplatin drug therapy, there was a direct relationship between DNA damage in leukocytes and disease response (summary two-sided p = 0.00011). The cohort of patients had 15 different tumor types, suggesting that blood tissue and tumor tissue of an individual may process platinum-DNA damage similarly regardless of the tissue of origin of the tumor. In leukocytes in vivo, persistence and accumulation were prominent features of the cisplatin-DNA adduct profile. Functional DNA repair capacity has been studied in eight human leukocyte cell lines in vitro (three, T-cells; three, B-cells; one, monocytic; one, promyelocytic), using a host cell reactivation assay with-cisplatin-damaged pRSVcat. In the three T cell lines studied, host cell reactivation efficiency was directly related to the cells' abilities to repair cisplatin-damaged cellular DNA (correlation coefficient = 0.993). These data suggest that blood tissue and tumor tissue may process platinum-DNA adducts similarly on a molecular level and that human T lymphocytes are a suitable target for a prospective study of the impact of DNA repair on clinical response to platinum compounds.

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Section: Introductionmentioning

confidence: 99%

Cisplatin-DNA Damage and Repair in Peripheral Blood Leukocytes in Vivo and in Vitro

Dabholkar¹,

Bradshaw²,

Parker³

et al. 1992

Environmental Health Perspectives

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“…Whereas AAS measures total platinum bound to DNA, the cisplatin-DNA ELISA significantly underestimates the total amount of intrastrand DNA adducts. This observation was first made in samples from rats (19,20). Although ELISA measured only 0.2% ofthe total DNA-bound platinum determined by AAS, a linear correlation was observed between the two assays in kidneys ofrats exposed to increasing doses ofthe drug.…”

Section: Comparison Of Cisplatin-dna Elisa and Aas For Analysis Of Dnmentioning

confidence: 92%

“…The cisplatin-DNA ELISA was performed with a rabbit anticisplatin DNA using 35 lAg of DNA per well, as previously described (4,19). For each assay, a standard curve was generated using calf thymus DNA modified in vitro to a level of4.3 adducts per 100 nucleotides (determined by AAS).…”

Section: Cisplatin-dna Elisamentioning

confidence: 99%

Platinum Drug-DNA Interactions in Human Tissues Measured by Cisplatin-DNA Enzyme-Linked Immunosorbent Assay and Atomic Absorbance Spectroscopy

Poirier¹,

Reed²,

Shamkhani³

et al. 1993

Environmental Health Perspectives

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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 (ELUSA), which detects a fraction of the AAS-measurable adduct. These studies were designed to explore mechanisms ofdrug-DNA interactions, to make correlations with clinical outcome, and possibly to validate DNA adduct measurements for use in occupational and environmental bioHmoitoring. The resls, 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 ticity. Platinum was also observed bound to ovarian tumor DNA. The adducts were highly persistent, being measurable in tissues obtained at autopsy upto 15 months after the last administration of platinum chemotherapy. A comparison ofbood 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.

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“…The conversion factor of 0.2% (or, 500-fold) was used as discussed above [66], to convert adduct levels assayed by ELISA to adduct levels assayed by AAS. When the data of Poirier is converted to 'AAS equivalents', a striking pattern becomes apparent, as shown in Table VI.…”

Section: Evidence That Dna Damage Is Important In the Clinicmentioning

confidence: 99%

Nucleotide excision repair and anti-cancer chemotherapy

Reed¹

1998

Multiple Drug Resistance in Cancer 2

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DNA repair is an important effector of anti-cancer drug resistance. In recent years, it has become apparent that DNA repair is an extremely complex process. Processes within DNA repair that may contribute to one or more drug resistance phenotypes include; O-6-alkyltransferase activity, base excision repair, mismatch repair, nucleotide excision repair, and gene specific repair. Clearly, several of these processes may show increased activity within any single cell, or tumor, at any one time. This review attempts to touch briefly upon the question of the distinctions between each of these specific pathways; and then seeks to expand on nucleotide excision repair as a possible effector of cellular and clinical resistance to platinum-based anticancer therapy.

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Characterization of the DNA damage recognized by the antiserum elicited against cis-diamminedichloroplatinum (II)-modified DNA

Cited by 23 publications

References 0 publications

Cisplatin-DNA Damage and Repair in Peripheral Blood Leukocytes in Vivo and in Vitro

Cisplatin-DNA Damage and Repair in Peripheral Blood Leukocytes in Vivo and in Vitro

Platinum Drug-DNA Interactions in Human Tissues Measured by Cisplatin-DNA Enzyme-Linked Immunosorbent Assay and Atomic Absorbance Spectroscopy

Nucleotide excision repair and anti-cancer chemotherapy

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