The quantitative detection of various Pt-DNA-adducts in Chinese hamster ovary cells treated with cisplatin: application of immunochemical techniques

Plooy, Adrie C.M.; Fichtinger-Schepman, Anne Marie J.; Schutte, Henk H.; Dijk, Margriet van; Lohman, P.H.M.

doi:10.1093/carcin/6.4.561

Cited by 87 publications

(25 citation statements)

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“…Moreover, an analogy was made between UV irradiation and ubiquitination of the large subunit of RNA Pol II, leading to proteolytic degradation and a decrease in the pool of RNA Pol II (5a). It has also to be kept in mind that any drug has side effects: for example, platinum derivatives provoke the formation of very low levels of protein-DNA cross-links in the cell (34).…”

Section: Discussionmentioning

confidence: 99%

TATA Binding Protein Discriminates between Different Lesions on DNA, Resulting in a Transcription Decrease

Coin

Frit

Viollet

et al. 1998

Molecular and Cellular Biology

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DNA damage recognition by basal transcription factors follows different mechanisms. Using transcriptioncompetition, nitrocellulose filter binding, and DNase I footprinting assays, we show that, although the general transcription factor TFIIH is able to target any kind of lesion which can be repaired by the nucleotide excision repair pathway, TATA binding protein (TBP)-TFIID is more selective in damage recognition. Only genotoxic agents which are able to induce kinked DNA structures similar to the one for the TATA box in its TBP complex are recognized. Indeed, DNase I footprinting patterns reveal that TBP protects equally 4 nucleotides upstream and 6 nucleotides downstream from the A-T (at position ؊29 of the noncoding strand) of the adenovirus major late promoter and from the G-G of a cisplatin-induced 1,2-d(GpG) cross-link. Together, our results may partially explain differences in transcription inhibition rates following DNA damage.Many carcinogens and antitumor agents structurally modify DNA, often at specific DNA sequences, with as a consequence the disturbance of mechanisms which govern cell life. Following DNA damage, one observes cell cycle arrests in G 2 /M and G 1 phases and a decrease in the rate of transcription. Investigations aimed at elucidating how cells respond to DNA damage evidenced a transcriptionally connected subpathway of DNA repair, called nucleotide excision repair (NER), in which lesions in transcribed genes were preferentially repaired (4,28). This connection between the two mechanisms was further and definitively established when it was demonstrated that the multiprotein complex TFIIH, essential for protein-encoding gene transcription, was also fundamental for NER (for reviews, see references 16 and 36).One of the first steps of any repair process is recognition of the damage, and thus, significant studies have been devoted to identifying proteins able to bind specifically to cisplatin-or UV-induced lesions (for a review, see reference 5). In an effort to understand how TFIIH shuttles between the transcription template and the DNA lesion, we surprisingly demonstrated that TATA binding protein (TBP)-TFIID, another essential basal transcription factor which normally recognizes the TATA box sequence located 30 bp upstream from the transcription start site, also interacts with damaged DNA (41).Before trying to understand the putative role of TBP in DNA repair, we considered it worthwhile to expand our investigations examining the connection between these two essential transcription components, TFIIH and TFIID, and several damaged DNAs. Seven different drugs ( Fig. 1 and Table 1) which bind covalently to DNA were chosen. The platinum derivatives form mono-or bifunctional adducts with DNA. First, the diethylenetriaminedichloroplatinum(II) derivative (Dien) (24) was chosen for its ability to form a monofunctional adduct recognized by the NER pathway in bacteria (2). Cisplatin (CDDP), transplatin (TDDP), and dachplatin (Dach) were used for their capacity to induce monofunctional adducts which ...

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Section: Discussionmentioning

confidence: 99%

TATA Binding Protein Discriminates between Different Lesions on DNA, Resulting in a Transcription Decrease

Coin

Frit

Viollet

et al. 1998

Molecular and Cellular Biology

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“…The same studies, however, also showed differences in DNA platination between various organs and human tissues from the same patients. Fichtinger-Schepman et al (1985, 1989) used antibodies raised against synthetic haptens mimicking the Pt-containing digestion products of DNA to detect the various Pt-DNA adducts after chromatography of enzymatically digested DNA samples, also by use of the ELISA (Plooy et al, 1985). They also reported higher Pt-DNA adduct levels in the leucocytes of testicular cancer patients who showed a complete tumour response than in the leucocytes of those with a partial response or progressive disease.…”

Section: Discussionmentioning

confidence: 99%

“…The development of antisera against platinated DNA has opened the way for the detection of low-level Pt-DNA adducts in human material (Poirier et al, 1982;Lippard et al, 1983;Fichtinger-Schepman et al, 1985;Plooy et al, 1985;Sundquist et al, 1987;Terheggen et al, 1987Terheggen et al, , 1991Tilby et al, 1991;Chao et al, 1994). Until now, no serial measurements of Pt-DNA adducts have been performed in tumour cells of CDDP-treated patients.…”

Section: Discussionmentioning

confidence: 99%

Immunocytochemical analysis of cisplatin-induced platinum-DNA adducts with double-fluorescence video microscopy

Meijer

Vries²,

Dam³

et al. 1997

Br J Cancer

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SummaryTo detect low-level DNA platination, a sensitive immunocyto-and histochemical technique was developed using a polyclonal antibody. The antibody GPt, derived after immunization of rabbits with highly platinated DNA and purified with affinity chromatography, detected the main platinum (Pt)-containing intrastrand and interstrand adducts. Double-fluorescence microscopy image analysis was used to quantify Pt-DNA adducts with Hoechst 33258 fluorescence to locate the nuclei and with fluorescein isothiocyanate fluorescence to measure the immunosignal. A two-to five-fold dose-dependent difference in the level of cisplatin (CDDP)-induced Pt-DNA adducts between a CDDPsensitive and -resistant human tumour cell line was detected. Large differences in Pt-DNA adduct levels after in vitro CDDP incubation between human buccal cells, lymphocytes and biopsies of different tumour types were observed. Pt-DNA adduct levels were fivefold higher in human testicular tumours than in colon tumours, representing CDDP-sensitive and -resistant tumours, respectively, in the clinic. These data suggest the possibility of predictive testing by measuring Pt-DNA adduct levels. Pt-DNA adducts in patients after treatment with CDDP were shown in normal buccal cells and in imprints of fresh tumour biopsies as well as in paraffin-embedded tumour cells. The analysis of Pt-DNA adducts at a single-cell level in small samples of normal and tumour cells during and/or after treatment is feasible with GPt and will hopefully enable more selective treatment of patients.Keywords: cisplatin; platinum-DNA adducts; immunocytochemistry; histochemistry; polyclonal antibody; image analysis CDDP and its analogues are among the most important chemotherapeutic drugs in clinical practice with a broad spectrum of activity. Almost all patients treated for testicular cancer with CDDP-containing combinations respond, and approximately 80% are cured. In contrast, no cures can be obtained in the case of colon cancer and most other solid tumours, even when initially sensitive to this drug, for example in the case of small-cell lung cancer (Loehrer and Einhorn, 1984). In all of these settings, a number of patients will not respond to therapy, although side-effects will be similar to those of responders. It would be desirable to be able to predict response to therapy as, for non-responders, either dose intensification or other forms of treatment would be preferable to standard CDDP treatment.In the past, rather unsuccessful attempts have been made to predict responses to therapy. Studies were performed with detection methods for cell kill (Hamburger and Salmon, 1977) or proliferation inhibition (Mosman, 1983; Weisenthal et al, 1983) in solid tumour samples exposed to drugs in vitro. Attempts to predict the effects of treatment of childhood lymphoblastic leukaemia by exposure of (non-proliferating) peripheral blood blast cells in vitro to drugs before systemic treatment have been more successful (Pieters et al, 1991). For (Poirier et al, 1985(Poirier et al, , 1992Reed et...

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“…The spectrum of adducts found between CDDP and DNA (Pt-GG, Pt-AG, Pt-GMP and G-Pt-G) does not differ between isolated DNA and various cell types (FichtingerSchepman et al, 1985(FichtingerSchepman et al, , 1987(FichtingerSchepman et al, , 1988Bedford et al, 1988;Plooy et al, 1985). However, quantitative differences exist between adducts found in different cell lines with widely different sensitivity for cisplatin .…”

Section: Discussionmentioning

confidence: 99%

The formation and removal of cisplatin (CDDP) induced DNA adducts in a CDDP sensitive and resistant human small cell lung carcinoma (HSCLC) cell line

Hospers

Vries²,

Mulder³

1990

Br J Cancer

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In DNA digested samples of CDDP sensitive (GLC4) and an 11-fold resistant (GLC4-CDDP) hSCLC line, the CDDP induced DNA adducts Pt-GG (Pt-(NH3)2d (pGpG], Pt-AG (Pt-(NH3)2d (pApG], G-Pt-G (Pt-(NH3)2d (GMP)2) and Pt-GMP (Pt-(NH3)3d GMP), were measured with polyclonal antibodies. The total amount of platinum (Pt) bound to DNA was also measured but with the help of atomic absorption spectroscopy (AAS). An increased net formation in GLC4 compared with GLC4-CDDP is found for the total Pt bound to DNA, Pt-GG and Pt-AG adducts after a 2 h 100 microM CDDP treatment. No significant difference is detected in the net formation of the Pt-GMP and G-Pt-G adducts. A slow Pt-AG adduct formation, with a maximum reached 10 h after CDDP composition, is found for both cell lines. In the 22 h period after the 2 h 100 microM CDDP treatment, a significant removal in GLC4 is measured for the Pt-GG, Pt-AG and the Pt-GMP adducts. For GLC4-CDDP a significant removal is detected in the total Pt bound to DNA, the Pt-AG and the Pt-GMP adducts. The removal of the total Pt bound to DNA in GLC4-CDDP cannot be explained by an adduct measured with the immunochemical method. In conclusion, no evidence is found that CDDP resistance is based upon the repair of the Pt-GG, Pt-AG, G-Pt-G and Pt-GMP adducts.

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The quantitative detection of various Pt-DNA-adducts in Chinese hamster ovary cells treated with cisplatin: application of immunochemical techniques

Cited by 87 publications

References 0 publications

TATA Binding Protein Discriminates between Different Lesions on DNA, Resulting in a Transcription Decrease

TATA Binding Protein Discriminates between Different Lesions on DNA, Resulting in a Transcription Decrease

Immunocytochemical analysis of cisplatin-induced platinum-DNA adducts with double-fluorescence video microscopy

The formation and removal of cisplatin (CDDP) induced DNA adducts in a CDDP sensitive and resistant human small cell lung carcinoma (HSCLC) cell line

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