Abstract:
:This study was designed to compare radiosensitization by the oral platinum compound JM216 with cisplatin. RIF1 mouse tumour cells were treated at various doses and at various exposure times with JM216 and irradiated 15 min before the end of drug exposure. The fraction of cells surviving treatment was assessed by colony formation. Results were compared with those for equivalent treatments with cisplatin. JM216 alone showed exponential killing of RIF1 cells, being approximately three times less efficient than cisplatin on a molar basis. For radiosensitization studies, drug doses used gave approximately 50 or 90% cell killing alone. No radiosensitization was seen after 2-h drug exposures, but significant radiosensitization occurred after 1- and 0.5-h exposures (shorter times required proportionally higher drug doses, giving equivalent drug kill). The enhancement ratio and time dependence were similar for the two platinum compounds, reaching 1.5 at the highest concentrations tested. Drug DNA adduct formation was assessed using immunocytochemistry with the NKI-A59 antiserum raised to cisplatin-DNA adducts. The antiserum was shown to recognize JM216-DNA adducts in a dose-dependent manner and maximum nuclear staining was found to be correlated with cell kill for both drugs. However, neither the level of staining at the time of irradiation nor at the time of maximum adducts correlated with radiosensitization, indicating that the number of DNA adducts did not determine radiosensitization. Intracellular glutathione levels were shown to be decreased by the drug, but only by approximately 50%, implying that this was not the cause of the increased radiosensitivity. In summary, JM216 was shown capable of radiosensitizing a platinum-sensitive tumour line to an extent similar to cisplatin. Radiosensitization was exposure-time and drug-concentration dependent, but was not dependent on DNA adduct levels nor glutathione depletion. In contrast, cell kill after drug alone was well correlated with adduct levels. These data suggest that JM216 could replace cisplatin in combined radiotherapy-chemotherapy studies, and also indicate that the NKI-A59 antibody could be used to monitor exposure levels in vivo.
journal_name
Int J Radiat Bioljournal_title
International journal of radiation biologyauthors
van de Vaart PJ,Klaren HM,Hofland I,Begg ACdoi
10.1080/095530097142834subject
Has Abstractpub_date
1997-12-01 00:00:00pages
675-83issue
6eissn
0955-3002issn
1362-3095journal_volume
72pub_type
杂志文章abstract::Cultures of JU-56 cells were irradiated in either G1 or G2 and examined either in their first post-irradiation metaphase (in diploids) or in their second post-irradiation metaphase (in colcemid-induced tetraploids). The timing of fixation, together with tritiated thymidine pulse labelling, allowed selection for scorin...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009314552131
更新日期:1993-06-01 00:00:00
abstract:PURPOSE:The low dose (<1 Gy) survival curve of mammalian cells is characterized by a region of hypersensitivity (HRS) followed by increased resistance (IRR). Above 1 Gy, the survival response can be described with a smooth downward-bending curve. Indirect evidence has indicated that the IRR response might reflect an in...
journal_title:International journal of radiation biology
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abstract:PURPOSE:To investigate whether extremely low frequency electromagnetic field (ELF-EMF) exposure could induce oxidative stress in workers performing tour-inspection near transformers and distribution power lines. MATERIALS AND METHODS:Occupational short-term 'spot' measurements were performed. In total, 310 inspection ...
journal_title:International journal of radiation biology
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更新日期:2015-05-01 00:00:00
abstract::Purpose To study the effect of microwave (MW) irradiation and consistent action of microwaves and static magnetic field (MF) on the giant chromosomes endoreduplication in Drosophila melanogaster Meig. Materials and methods Experiments were carried out on inbred wild type Canton-S strain. Exposure to microwaves (freque...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2016.1137105
更新日期:2016-01-01 00:00:00
abstract::The yields of strand break formation (Gssb) in single-stranded DNA (ssDNA) initiated by radiation-generated OH radicals have been determined using the method of low-angle laser light scattering (LALLS). The irradiations were carried out in aqueous, N2O-saturated solutions in the absence and presence of oxygen and at d...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009014551951
更新日期:1990-10-01 00:00:00
abstract::Chinese hamster ovary cells were exposed to various heat treatments followed by X-irradiation, and the induction and repair of DNA strand breaks was studied using the alkaline unwinding technique. Heat treatments alone were found to cause DNA strand breakage only for temperatures greater than or equal to 43 degrees C,...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009214550851
更新日期:1992-02-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553000410001723866
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:Testicular seminoma cancer incidence has significantly increased over the last few decades, and although it is successfully treated by radiotherapy, long-term health risks are still unclear. The aim of the study was to show long-term genome damage in patients with seminoma after radiotherapy. MATERIALS AND MET...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2013.825057
更新日期:2013-11-01 00:00:00
abstract::Solid human tumours contain areas with low oxygen tension (pO2). For bioreductive drugs it is important to define the cytotoxic effect according to drug concentration and to clinically relevant pO2. In this study, the pO2 dependence of the survival of three human cell lines (HRT 18, Na11 +, and MEWO), exposed to tirap...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009514550261
更新日期:1995-02-01 00:00:00
abstract::The effects of a low dose (0.1-20 mGy) preirradiation with X-rays followed by a higher dose (2 Gy) of the same radiation on the recovery of the genetic damage induced as dominant lethals in mature oocytes (stage 14) of different strains of Drosophila melanogaster were investigated. The response was shown to be depende...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009414550501
更新日期:1994-04-01 00:00:00
abstract:PURPOSE:Multicellular tumour spheroids are being used with increasing frequency in various aspects of tumour biology, including studies dealing with radiation biology. This review attempts to outline recent studies using these three-dimensional systems in radiation biology with particular reference made to papers testi...
journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/095530099139845
更新日期:1999-07-01 00:00:00
abstract::Only a small percentage of the DNA damage set by ionizing radiation in the living cell manifests itself as lethal. It is now increasingly accepted that clustered lesions may constitute the kind of damage that the repair enzymes cannot adequately deal with. The question is raised as to whether damage amplification reac...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009414551501
更新日期:1994-11-01 00:00:00
abstract::Purpose: Projects evaluating the effects of radiation, within the National Institutes of Quantum and Radiological Science and Technology (QST), National Institute of Radiological Sciences (NIRS), have focused on risk analyses for life shortening and cancer prevalence using laboratory animals. Genetic and epigenetic al...
journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/09553002.2019.1625458
更新日期:2019-10-01 00:00:00
abstract::Cell cycle dependence for the induction of 6-thioguanine-resistant mutation was investigated using synchronized mouse L5178Y cells after exposure to 4 Gy to 60Co gamma-rays or 1 Gy of 252Cf radiation (fission neutrons). Maximal mutation frequency was observed immediately after release from colcemid block (G2/M phase) ...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009314550631
更新日期:1993-04-01 00:00:00
abstract:PURPOSE:To reduce retention and toxicity of the alpha particle emitter polonium-210 in rats by newly developed chelating agents. MATERIALS AND METHODS:Repeated subcutaneous chelation was conducted after intravenous injection of 210Po nitrate. For reduction of 210Po retention the treatment with vicinal dithiols meso-an...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553000050151691
更新日期:2000-10-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553000210126466
更新日期:2002-07-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2013.817706
更新日期:2013-12-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/095530000138349
更新日期:2000-05-01 00:00:00
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journal_title:International journal of radiation biology
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doi:10.1080/095530099139944
更新日期:1999-07-01 00:00:00
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更新日期:1998-06-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章
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更新日期:2003-11-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009514550661
更新日期:1995-05-01 00:00:00
abstract:PURPOSE:To resolve the difficulty in counting merged DNA damage foci in high-LET (linear energy transfer) ion-induced patterns. MATERIALS AND METHODS:The analysis of patterns of RIF (radiation-induced foci) produced by high-LET Fe and Ti ions were conducted by using a Monte Carlo model that combines the heavy ion trac...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553001003717175
更新日期:2010-06-01 00:00:00
abstract::We have examined the timing of gamma-irradiation-induced death in relation to cell cycle progression using a panel of mouse lymphoid or myeloid cell lines. Death was found to occur immediately after irradiation ('rapid interphase' death), or after arrest in G2 phase ('delayed interphase' death). In part II of this ser...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009414550261
更新日期:1994-02-01 00:00:00
abstract:PURPOSE:To honour perhaps the most influential man in the radiation sciences, Henry S. Kaplan, by reviewing the field of tumour hypoxia, one of his many interests. RESULTS:It was postulated over 50 years ago by Thomlinson and Gray that human solid tumours would contain hypoxic cells and that they would exert a negativ...
journal_title:International journal of radiation biology
pub_type: 历史文章
doi:10.3109/09553002.2010.492492
更新日期:2010-11-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.3109/09553002.2014.911988
更新日期:2014-10-01 00:00:00
abstract::Sister chromatid exchanges (SCEs) were analysed in lymphocytes from 12 control persons and 33 Chernobyl clean-up workers. The group of Chernobyl clean-up workers consisted of civilians who were forced to go to Chernobyl to clean up environmental contamination caused by Chernobyl disaster. On average, they received 0.1...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009514550791
更新日期:1995-06-01 00:00:00
abstract::Swiss albino mice (7-8 weeks old) were irradiated with different doses (0-25 Gy) of gamma-radiation at a dose-rate of 0.05 Gy/s. The specific activities of glyoxalase I (GI) and glyoxalase II (GII) were determined in the spleen and liver immediately and on the 3rd and 6th day postirradiation. The results indicate that...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009314550301
更新日期:1993-02-01 00:00:00
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journal_title:International journal of radiation biology
pub_type: 杂志文章,评审
doi:10.1080/09553009014550961
更新日期:1990-04-01 00:00:00
abstract::BW12C, which was developed as an agent for the treatment of sickle cell anaemia, increases the binding of oxygen to haemoglobin and hence reduces the availability of oxygen to tissues. Due to these changes in oxygen availability BW12C could act as a protector against radiation-induced injury to normal tissues. In this...
journal_title:International journal of radiation biology
pub_type: 杂志文章
doi:10.1080/09553009114550921
更新日期:1991-04-01 00:00:00