Trevor McMillan - Academia.edu (original) (raw)
Papers by Trevor McMillan
European Journal of Cancer, 1993
Springer eBooks, 1996
Part 1 Oncogenes: 1. What are cancer genes and how do they upset cell behaviour? (J. Yarnold). 2.... more Part 1 Oncogenes: 1. What are cancer genes and how do they upset cell behaviour? (J. Yarnold). 2. Mechanisms of activation and inactivation of dominant oncogenes and tumour suppressor genes (M. Stratton). 3. Approaches to proto-oncogene and tumour suppressor gene identification (H. Patterson). 4. Transgenic modelling of dominant and recessive oncogene function (F.S. Pardo, E.V. Schmidt). 5. The BCL2 gene in clinical oncology (M. Brada, M. Dyer). 6. Identification and significance of EGFR and erbB2 overexpression (D.P. Hollywood, W.J. Gullick). 7. GTP-binding proteins and cancer (J. Downward). 8. The p53 gene in human cancer (M. Stratton). 9. Inherited predispositions to cancer - applications of molecular biology (V.A. Murday). 1O. Multistage carcinogenesis (A.H. Wyllie). 11. Human papillomavirus and cervical cancer (R C. Davies, K.H. Vousden). 12. Cell-cycle control and cancer (A.M. Carr). 13. Differentiation and cancer (M.D. Mason). Part 2 Therapeutics: 14. Molecular aspects of radiation sensitivity (C. Mort, T.J. McMillan). 15. Cells differ in their susceptibility to DNA damage induction and in their ability to repair it (S.J. Whitaker). 16. How do cells repair DNA damage? (G. Ross). 17. The isolation of DNA repair genes (R. Cartwright, T.J. McMillan). 18. Radiation-induced cytokines and growth factors: cellular and molecular basis of the modification of radiation damage (R. Weichselbaum et al). 19. Chemotherapeutic drug-induced DNA damage and repair (R. Brown, D. Bisset). 20. The molecular biology of drug resistance (D. Hochhauser). 21. Antibody technology is being transformed (R.E. Hawkins, S.J. Russell). 22. Prospects for gene therapy of cancer (J.D. Harris, K. Sikora). Part 3 Gene Structure and Techniques: 23. Introduction to gene structure and techniques (R. Wooster). 24. Chromatin structure and nuclear function (A.B. Hassan, D.A. Jackson). 25. The PCR revolution (R.A. Eeles, W. Warren, A. Stamps). 26. Techniques of molecular biology (P.J. Rocques).
European Journal of Cancer, 1992
Phase I trial of a mouse 28. monoclonal antibody against GD3 ganglioside in patients with melanom... more Phase I trial of a mouse 28. monoclonal antibody against GD3 ganglioside in patients with melanoma: induction of inflammatory responses at tumor sites. 3
British Journal of Cancer, 1990
The current use of targeted radiotherapy in the treatment of neuroblastoma has generated a requir... more The current use of targeted radiotherapy in the treatment of neuroblastoma has generated a requirement for further information on the radiobiology of these cells. Here we report on studies of the dose-rate effect in two human neuroblastoma cell lines (HX138 and HX142) and the recovery that they demonstrate in split-dose experiments. The sensitivity of the two cell lines to high dose-rate irradiation was confirmed. Surviving fractions at 2 Gy were 0.083 for HX138 anc' 0.11 for HX142. There was little evidence of a dose-rate effect above 2 cGy min-' but significant sparing was seen at lower dose rates. Substantial recovery was seen in split-dose experiments on both cell lines, to an extent that was consistent with the linear quadratic equation. The data were used to derive values for the P parameter of the linear-quadratic equation; the values for the neuroblastomas were higher than for any of the other human tumour cell lines that we have investigated to date. Thus, despite their high sensitivity to ionising radiation HX138 and HX142 do exhibit substantial levels of cellular recovery, suggesting that they may have a significant capacity for repair of radiation-induced lesions.
British Journal of Cancer, 1994
The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitiv... more The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitivity was studied in human breast and bladder cancer cell lines. Cell survival was measured by monolayer colony-forming assay as appropriate and differences in radiosensitivity were seen (a-values ranged from 0.12 to 0.54). After pulsed-field gel electrophoresis (PFGE) the initial slopes of dose-response curves were biphasic with a flattening of the curves above 30 Gy. When the frequency of DNA dsb induction was assessed using a mathematical model based on the DNA fragment size distribution into the gel lane, we found a statistically significant relationship between the number of DNA dsb induced and the corresponding a-values and fraction surviving after 2Gy (P = 0.0049 and P = 0.0031 respectively). These results support the view that initial damage is a major determinant of cell radiosensitivity.
British Journal of Cancer, 1996
We examined the relationship between p53 levels before and after irradiation, radiation-induced c... more We examined the relationship between p53 levels before and after irradiation, radiation-induced cell cycle delays, apoptotic cell death and radiosensitivity in a panel of eight human tumour cell lines. The cell lines differed widely in their clonogenic survival after radiation, (surviving fraction at 2 Gy: SF2 = 0.18-0.82). Constitutive p53 protein levels varied from 2.2 +0.4 to 6.3+0.3 optical density units (OD) per 106 cells. p53 after irradiation (6 Gy) also varied between the cell lines, ranging from no induction to a 1.6-fold increase in p53 levels 4 h after treatment. p53 function was also assessed by GI cell cycle arrest after irradiation. The cellular response to radiation, measured as GO/GI arrest, and the induction of apoptosis were in good agreement. However, a trace amount of DNA ladder formation was found in two cell lines lacking GI arrest. Overall cellular radiosensitivity correlated well with the level of radiation-induced GI arrest (correlation coefficient r=0.856; P=0.0067), with p53 constitutive levels (r=0.874, P=0.0046), and with p53 protein fold induction (r=-0.882, P=0.0038). Our data suggest that (1) the constitutive p53 level, (2) GI arrest after irradiation, or (3) the p53 protein response to radiation may be good predictive tests for radiosensitivity in some cell types.
British Journal of Cancer, 1995
Smm_ary Five established human breast cancer cell lines and one established human bladder cancer ... more Smm_ary Five established human breast cancer cell lines and one established human bladder cancer cell line of varying radiosensitivity have been used to determine whether the rejoining of DNA double-strand breaks (dsbs) shows a correlation with radiosensitivity. The kinetics of dsb rejoining was biphasic and both components proceeded exponentially with time. The half-time (t, j of rejoining ranged from 18.0 ± 1.4 to 36.4 ± 3.2 min (fast rejoining process) and from 1.5 ± 0.2 to 5.1 ± 0.2 h (slow rejoining process). We found a statistically significant relationship between the survival fraction at 2 Gy (SF2) and the t, of the fast rejoining component (r = 0.949, P = 0.0039). Our results suggest that cell lines which show rapid rejoining are more radioresistant. These results support the view that, as well as the level of damage induction that we have reported previously, the repair process is a major determinant of cellular radiosensitivity. It is possible that the differences found in DNA dsb rejoining and the differences in DNA dsb induction are related by a common mechanism, e.g. conformation of chromatin in the cell. Keywords radiosensitivity; DNA double-strand breaks; dsb rejoining; pulsed field gel electrophoresis
There is good evidence that the biological effects of UVA are mediated by certain reactive oxygen... more There is good evidence that the biological effects of UVA are mediated by certain reactive oxygen species (ROS) generated by hitherto unidentified photosensitisers within the cell. With the aim of identifying factors which modify the cellular response to UVA, we have developed an assay to detect such oxidative species utilising chemical probes which become fluorescent upon oxidation. Using a human bladder carcinoma cell line (MGH-U1) and spontaneously immortalised keratinocytes (HaCaT), we have shown a UVA (narrow band 365 2 5nm) dose-dependent increase in fluorescence by flow cytometry following loading of the cells with either dihydrorhodamine (DHR, 10pM) or 2',7'-dichlorofluorescin diacetate (DCFH-DA, 5yM). Spectrofluorimetric measurements demonstrated that the total fluorescence produced in the cells was 7.2 times greater than that produced by irradiating the probe in buffer alone indicating that the majority of probe oxidation is due to ROS generated by UVA. Incubation with buthionine-S,R-sulfoximine (BSO), an inhibitor of A-glutamylcysteine synthetase, reduced cellular glutathione (GSH) levels by upto 74% (mean of 6 measurements) in both cell lines and resulted in an increase in the +UV/-UV ratio (relative to a value of 1.00 for untreated cells) to 1.3320.07(mean) in DCFH-loaded HaCat cells and 1.420.076 in MGH-U1 cells, following treatment with 10kM BSO. Our data therefore point to the involvement of glutathione in modulating the level of UVA-induced free radicals.
The radioresistant RT112 and the radiosensitive HX-142 human tumour cell lines were examined in o... more The radioresistant RT112 and the radiosensitive HX-142 human tumour cell lines were examined in order to characterize the relative role which soluble compounds and DNA associated-proteins play in cellular protection against gamma rays. DNA double-strand breaks were measured using pulsed-field gel electrophoresis when cells were irradiated after lysis in solutions containing various salt concentrations. Differences between the two cell lines were found in the protective effect that soluble and DNA-associated compounds offer against damage induced by gamma irradiation. Unlike HX-142, both the soluble scavengers and DNA-associated proteins were found to play an important role within the cellular defences in the radioresistant cell line RT112. These data implicate the soluble scavengers as being principally responsible for the differences in damage induction observed in intact cells from these cell lines. It is suggested that the various components of the cellular defences against free-...
Radiotherapy and Oncology, 1991
Baker et al. [Cancer Res. 46: 1263-1274, 1986] developed an adhesive tumour cell culture system (... more Baker et al. [Cancer Res. 46: 1263-1274, 1986] developed an adhesive tumour cell culture system (ATCCS) using a culture surface coated with a cell attachment matrix (CAM). The ability of CAM-coated plates to support the growth of cells from human tumour biopsies has been evaluated. Successful growth was obtained in 9/22 samples (41%), but fibroblasts, rather than tumour cells, grew in the majority. Comparison of CAM with other surfaces showed that CAM was no better for establishing tumour cell growth than the presence of feeder cells or an alternative attachment factor vitronectin.
Radiation Research, 2006
BioOne Complete (complete.BioOne.org) is a full-text database of 200 subscribed and open-access t... more BioOne Complete (complete.BioOne.org) is a full-text database of 200 subscribed and open-access titles in the biological, ecological, and environmental sciences published by nonprofit societies, associations, museums, institutions, and presses.
Journal of Pharmacy and Pharmacology, 2008
UVA should receive significant consideration as a human health risk as it is a large proportion o... more UVA should receive significant consideration as a human health risk as it is a large proportion of the solar spectrum that reaches the earth's surface and because of its ability to penetrate human skin. It is only relatively recently that this has been recognized and this previously under-researched part of the UV spectrum is becoming increasingly well characterized at doses that are quite low in relation to those experienced by humans. Absorption of UVA in a cell leads to the production of reactive oxygen and nitrogen species that can damage major biomolecules including DNA and membrane lipids. Various types of damage induced in these molecules lead to significant biological effects including cytotoxicity, mutations and alterations in cell signalling pathways. Longer-term effects such as persistent genomic instability and bystander effects have also been observed following UVA treatment of mammalian cells and, as with ionizing radiation, this changes some of the fundamental thi...
International Journal of Radiation Biology, 1992
Cellular recovery was assessed in two sublines of L5178Y murine lymphoma cells of differing radio... more Cellular recovery was assessed in two sublines of L5178Y murine lymphoma cells of differing radiosensitivity (LY-S and LY-A4) using low dose-rate irradiation and split-dose experiments. No increase in cell survival was observed in the LY-S cell line until the dose-rate was reduced to 2 cGy/min, whereas in the LY-A4 cell line 20 cGy/min was low enough to detect changes in survival. The extent of this change, as assessed by dose reduction factors at 2 logs of cell kill, was greater in the LY-A4 cell line. Fitting these data with the incomplete repair model of Thames led to anomalous values for the half-time of repair. In split-dose experiments the maximum observed recovery ratio increased as a function of dose in a manner that is consistent with the linear-quadratic equation. As was found previously with radiosensitive human tumour cells, the LY-S cell line showed more split-dose recovery at any given dose than the LY-A4 cell line.
International Journal of Radiation Biology, 1997
Institu te of Canc er Research , the spectrum of m utations induced by radiation, (2) 15 Cotsw ol... more Institu te of Canc er Research , the spectrum of m utations induced by radiation, (2) 15 Cotsw old Road , Sutton SM 2 5N G , U K. to asses the dose± rate dep endence of the m utation ² P® zer, Sand w ich, Kent CT13 9N J, U K. spectra, and (3) to elucidate a possible m olecu lar Division of B iologic al Sciences, Canc er Sciences, Institu te of basis for the diå erence in sensitivity in M G H-U 1 Environm ental and B iologic al Sciences,
European Journal of Cancer, 1995
The overall survival by the Kaplan Meier estimate at 2 years is 79.3% with a median follow up of7... more The overall survival by the Kaplan Meier estimate at 2 years is 79.3% with a median follow up of7. 75 months and the progression free survival is 58% in the whole group of 73 patients. Interferon (inf) maintenance was started at a median of 61 days in 58/73 patients. We therefore conclude that the previously untreated group is a better risk group with respect to achieving remission as well as rapid engraftment. Inf was also started earlier in the untreated group. Longer follow up will be required however to comment on the efficacy of PBSCT. A CR rate of 55% in previously untreated patients is lower than our previously reported CR rate with ABMT in a comparable group ofpatients and the possibility of contamination of the stem cell grafts with myeloma should be borne in mind.
European Journal of Cancer, 1995
The British Journal of Radiology, 2006
XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation grou... more XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation group C. The patient was unusual in presenting with an angiosarcoma of the scalp, treated by surgical excision and radiotherapy. Following 38 Gy in 19 fractions with 6 MEV electrons, a severe desquamation and necrosis of the underlying bone ensued, and death followed 4 years later. The cell line was correspondingly hypersensitive to the lethal effects of gamma irradiation. We had previously shown that this sensitivity could be discriminated from that seen in ataxia-telangiectasia (A-T). The cellular response to ultraviolet radiation below 280 nm (UVC) was characteristic of XP cells, indicating the second instance, in our experience, of dual cellular UVC and ionizing radiation hypersensitivity in XP. We then set out to evaluate any defects in repair of ionizing radiation damage and to verify any direct contribution of the XPC gene. The cells were defective in repair of a fraction of double strand breaks, with a pattern reminiscent of A-T. The cell line was immortalized with the vector pSV3neo and the XPC cDNA transfected in to correct the defect. The progeny derived from this transfection showed the presence of the XPC gene product, as measured by immunoblotting. A considerable restoration of normal UVC, but not ionizing radiation, sensitivity was observed amongst the clones. This differential correction of cellular sensitivity is strong evidence for the presence of a defective radiosensitivity gene, distinct from XPC, which is responsible for the clinical hypersensitivity to ionizing radiation. It is important to resolve how widespread ionizing radiation sensitivity is amongst XP patients.
European Journal of Cancer, 1993
Springer eBooks, 1996
Part 1 Oncogenes: 1. What are cancer genes and how do they upset cell behaviour? (J. Yarnold). 2.... more Part 1 Oncogenes: 1. What are cancer genes and how do they upset cell behaviour? (J. Yarnold). 2. Mechanisms of activation and inactivation of dominant oncogenes and tumour suppressor genes (M. Stratton). 3. Approaches to proto-oncogene and tumour suppressor gene identification (H. Patterson). 4. Transgenic modelling of dominant and recessive oncogene function (F.S. Pardo, E.V. Schmidt). 5. The BCL2 gene in clinical oncology (M. Brada, M. Dyer). 6. Identification and significance of EGFR and erbB2 overexpression (D.P. Hollywood, W.J. Gullick). 7. GTP-binding proteins and cancer (J. Downward). 8. The p53 gene in human cancer (M. Stratton). 9. Inherited predispositions to cancer - applications of molecular biology (V.A. Murday). 1O. Multistage carcinogenesis (A.H. Wyllie). 11. Human papillomavirus and cervical cancer (R C. Davies, K.H. Vousden). 12. Cell-cycle control and cancer (A.M. Carr). 13. Differentiation and cancer (M.D. Mason). Part 2 Therapeutics: 14. Molecular aspects of radiation sensitivity (C. Mort, T.J. McMillan). 15. Cells differ in their susceptibility to DNA damage induction and in their ability to repair it (S.J. Whitaker). 16. How do cells repair DNA damage? (G. Ross). 17. The isolation of DNA repair genes (R. Cartwright, T.J. McMillan). 18. Radiation-induced cytokines and growth factors: cellular and molecular basis of the modification of radiation damage (R. Weichselbaum et al). 19. Chemotherapeutic drug-induced DNA damage and repair (R. Brown, D. Bisset). 20. The molecular biology of drug resistance (D. Hochhauser). 21. Antibody technology is being transformed (R.E. Hawkins, S.J. Russell). 22. Prospects for gene therapy of cancer (J.D. Harris, K. Sikora). Part 3 Gene Structure and Techniques: 23. Introduction to gene structure and techniques (R. Wooster). 24. Chromatin structure and nuclear function (A.B. Hassan, D.A. Jackson). 25. The PCR revolution (R.A. Eeles, W. Warren, A. Stamps). 26. Techniques of molecular biology (P.J. Rocques).
European Journal of Cancer, 1992
Phase I trial of a mouse 28. monoclonal antibody against GD3 ganglioside in patients with melanom... more Phase I trial of a mouse 28. monoclonal antibody against GD3 ganglioside in patients with melanoma: induction of inflammatory responses at tumor sites. 3
British Journal of Cancer, 1990
The current use of targeted radiotherapy in the treatment of neuroblastoma has generated a requir... more The current use of targeted radiotherapy in the treatment of neuroblastoma has generated a requirement for further information on the radiobiology of these cells. Here we report on studies of the dose-rate effect in two human neuroblastoma cell lines (HX138 and HX142) and the recovery that they demonstrate in split-dose experiments. The sensitivity of the two cell lines to high dose-rate irradiation was confirmed. Surviving fractions at 2 Gy were 0.083 for HX138 anc' 0.11 for HX142. There was little evidence of a dose-rate effect above 2 cGy min-' but significant sparing was seen at lower dose rates. Substantial recovery was seen in split-dose experiments on both cell lines, to an extent that was consistent with the linear quadratic equation. The data were used to derive values for the P parameter of the linear-quadratic equation; the values for the neuroblastomas were higher than for any of the other human tumour cell lines that we have investigated to date. Thus, despite their high sensitivity to ionising radiation HX138 and HX142 do exhibit substantial levels of cellular recovery, suggesting that they may have a significant capacity for repair of radiation-induced lesions.
British Journal of Cancer, 1994
The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitiv... more The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitivity was studied in human breast and bladder cancer cell lines. Cell survival was measured by monolayer colony-forming assay as appropriate and differences in radiosensitivity were seen (a-values ranged from 0.12 to 0.54). After pulsed-field gel electrophoresis (PFGE) the initial slopes of dose-response curves were biphasic with a flattening of the curves above 30 Gy. When the frequency of DNA dsb induction was assessed using a mathematical model based on the DNA fragment size distribution into the gel lane, we found a statistically significant relationship between the number of DNA dsb induced and the corresponding a-values and fraction surviving after 2Gy (P = 0.0049 and P = 0.0031 respectively). These results support the view that initial damage is a major determinant of cell radiosensitivity.
British Journal of Cancer, 1996
We examined the relationship between p53 levels before and after irradiation, radiation-induced c... more We examined the relationship between p53 levels before and after irradiation, radiation-induced cell cycle delays, apoptotic cell death and radiosensitivity in a panel of eight human tumour cell lines. The cell lines differed widely in their clonogenic survival after radiation, (surviving fraction at 2 Gy: SF2 = 0.18-0.82). Constitutive p53 protein levels varied from 2.2 +0.4 to 6.3+0.3 optical density units (OD) per 106 cells. p53 after irradiation (6 Gy) also varied between the cell lines, ranging from no induction to a 1.6-fold increase in p53 levels 4 h after treatment. p53 function was also assessed by GI cell cycle arrest after irradiation. The cellular response to radiation, measured as GO/GI arrest, and the induction of apoptosis were in good agreement. However, a trace amount of DNA ladder formation was found in two cell lines lacking GI arrest. Overall cellular radiosensitivity correlated well with the level of radiation-induced GI arrest (correlation coefficient r=0.856; P=0.0067), with p53 constitutive levels (r=0.874, P=0.0046), and with p53 protein fold induction (r=-0.882, P=0.0038). Our data suggest that (1) the constitutive p53 level, (2) GI arrest after irradiation, or (3) the p53 protein response to radiation may be good predictive tests for radiosensitivity in some cell types.
British Journal of Cancer, 1995
Smm_ary Five established human breast cancer cell lines and one established human bladder cancer ... more Smm_ary Five established human breast cancer cell lines and one established human bladder cancer cell line of varying radiosensitivity have been used to determine whether the rejoining of DNA double-strand breaks (dsbs) shows a correlation with radiosensitivity. The kinetics of dsb rejoining was biphasic and both components proceeded exponentially with time. The half-time (t, j of rejoining ranged from 18.0 ± 1.4 to 36.4 ± 3.2 min (fast rejoining process) and from 1.5 ± 0.2 to 5.1 ± 0.2 h (slow rejoining process). We found a statistically significant relationship between the survival fraction at 2 Gy (SF2) and the t, of the fast rejoining component (r = 0.949, P = 0.0039). Our results suggest that cell lines which show rapid rejoining are more radioresistant. These results support the view that, as well as the level of damage induction that we have reported previously, the repair process is a major determinant of cellular radiosensitivity. It is possible that the differences found in DNA dsb rejoining and the differences in DNA dsb induction are related by a common mechanism, e.g. conformation of chromatin in the cell. Keywords radiosensitivity; DNA double-strand breaks; dsb rejoining; pulsed field gel electrophoresis
There is good evidence that the biological effects of UVA are mediated by certain reactive oxygen... more There is good evidence that the biological effects of UVA are mediated by certain reactive oxygen species (ROS) generated by hitherto unidentified photosensitisers within the cell. With the aim of identifying factors which modify the cellular response to UVA, we have developed an assay to detect such oxidative species utilising chemical probes which become fluorescent upon oxidation. Using a human bladder carcinoma cell line (MGH-U1) and spontaneously immortalised keratinocytes (HaCaT), we have shown a UVA (narrow band 365 2 5nm) dose-dependent increase in fluorescence by flow cytometry following loading of the cells with either dihydrorhodamine (DHR, 10pM) or 2',7'-dichlorofluorescin diacetate (DCFH-DA, 5yM). Spectrofluorimetric measurements demonstrated that the total fluorescence produced in the cells was 7.2 times greater than that produced by irradiating the probe in buffer alone indicating that the majority of probe oxidation is due to ROS generated by UVA. Incubation with buthionine-S,R-sulfoximine (BSO), an inhibitor of A-glutamylcysteine synthetase, reduced cellular glutathione (GSH) levels by upto 74% (mean of 6 measurements) in both cell lines and resulted in an increase in the +UV/-UV ratio (relative to a value of 1.00 for untreated cells) to 1.3320.07(mean) in DCFH-loaded HaCat cells and 1.420.076 in MGH-U1 cells, following treatment with 10kM BSO. Our data therefore point to the involvement of glutathione in modulating the level of UVA-induced free radicals.
The radioresistant RT112 and the radiosensitive HX-142 human tumour cell lines were examined in o... more The radioresistant RT112 and the radiosensitive HX-142 human tumour cell lines were examined in order to characterize the relative role which soluble compounds and DNA associated-proteins play in cellular protection against gamma rays. DNA double-strand breaks were measured using pulsed-field gel electrophoresis when cells were irradiated after lysis in solutions containing various salt concentrations. Differences between the two cell lines were found in the protective effect that soluble and DNA-associated compounds offer against damage induced by gamma irradiation. Unlike HX-142, both the soluble scavengers and DNA-associated proteins were found to play an important role within the cellular defences in the radioresistant cell line RT112. These data implicate the soluble scavengers as being principally responsible for the differences in damage induction observed in intact cells from these cell lines. It is suggested that the various components of the cellular defences against free-...
Radiotherapy and Oncology, 1991
Baker et al. [Cancer Res. 46: 1263-1274, 1986] developed an adhesive tumour cell culture system (... more Baker et al. [Cancer Res. 46: 1263-1274, 1986] developed an adhesive tumour cell culture system (ATCCS) using a culture surface coated with a cell attachment matrix (CAM). The ability of CAM-coated plates to support the growth of cells from human tumour biopsies has been evaluated. Successful growth was obtained in 9/22 samples (41%), but fibroblasts, rather than tumour cells, grew in the majority. Comparison of CAM with other surfaces showed that CAM was no better for establishing tumour cell growth than the presence of feeder cells or an alternative attachment factor vitronectin.
Radiation Research, 2006
BioOne Complete (complete.BioOne.org) is a full-text database of 200 subscribed and open-access t... more BioOne Complete (complete.BioOne.org) is a full-text database of 200 subscribed and open-access titles in the biological, ecological, and environmental sciences published by nonprofit societies, associations, museums, institutions, and presses.
Journal of Pharmacy and Pharmacology, 2008
UVA should receive significant consideration as a human health risk as it is a large proportion o... more UVA should receive significant consideration as a human health risk as it is a large proportion of the solar spectrum that reaches the earth's surface and because of its ability to penetrate human skin. It is only relatively recently that this has been recognized and this previously under-researched part of the UV spectrum is becoming increasingly well characterized at doses that are quite low in relation to those experienced by humans. Absorption of UVA in a cell leads to the production of reactive oxygen and nitrogen species that can damage major biomolecules including DNA and membrane lipids. Various types of damage induced in these molecules lead to significant biological effects including cytotoxicity, mutations and alterations in cell signalling pathways. Longer-term effects such as persistent genomic instability and bystander effects have also been observed following UVA treatment of mammalian cells and, as with ionizing radiation, this changes some of the fundamental thi...
International Journal of Radiation Biology, 1992
Cellular recovery was assessed in two sublines of L5178Y murine lymphoma cells of differing radio... more Cellular recovery was assessed in two sublines of L5178Y murine lymphoma cells of differing radiosensitivity (LY-S and LY-A4) using low dose-rate irradiation and split-dose experiments. No increase in cell survival was observed in the LY-S cell line until the dose-rate was reduced to 2 cGy/min, whereas in the LY-A4 cell line 20 cGy/min was low enough to detect changes in survival. The extent of this change, as assessed by dose reduction factors at 2 logs of cell kill, was greater in the LY-A4 cell line. Fitting these data with the incomplete repair model of Thames led to anomalous values for the half-time of repair. In split-dose experiments the maximum observed recovery ratio increased as a function of dose in a manner that is consistent with the linear-quadratic equation. As was found previously with radiosensitive human tumour cells, the LY-S cell line showed more split-dose recovery at any given dose than the LY-A4 cell line.
International Journal of Radiation Biology, 1997
Institu te of Canc er Research , the spectrum of m utations induced by radiation, (2) 15 Cotsw ol... more Institu te of Canc er Research , the spectrum of m utations induced by radiation, (2) 15 Cotsw old Road , Sutton SM 2 5N G , U K. to asses the dose± rate dep endence of the m utation ² P® zer, Sand w ich, Kent CT13 9N J, U K. spectra, and (3) to elucidate a possible m olecu lar Division of B iologic al Sciences, Canc er Sciences, Institu te of basis for the diå erence in sensitivity in M G H-U 1 Environm ental and B iologic al Sciences,
European Journal of Cancer, 1995
The overall survival by the Kaplan Meier estimate at 2 years is 79.3% with a median follow up of7... more The overall survival by the Kaplan Meier estimate at 2 years is 79.3% with a median follow up of7. 75 months and the progression free survival is 58% in the whole group of 73 patients. Interferon (inf) maintenance was started at a median of 61 days in 58/73 patients. We therefore conclude that the previously untreated group is a better risk group with respect to achieving remission as well as rapid engraftment. Inf was also started earlier in the untreated group. Longer follow up will be required however to comment on the efficacy of PBSCT. A CR rate of 55% in previously untreated patients is lower than our previously reported CR rate with ABMT in a comparable group ofpatients and the possibility of contamination of the stem cell grafts with myeloma should be borne in mind.
European Journal of Cancer, 1995
The British Journal of Radiology, 2006
XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation grou... more XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation group C. The patient was unusual in presenting with an angiosarcoma of the scalp, treated by surgical excision and radiotherapy. Following 38 Gy in 19 fractions with 6 MEV electrons, a severe desquamation and necrosis of the underlying bone ensued, and death followed 4 years later. The cell line was correspondingly hypersensitive to the lethal effects of gamma irradiation. We had previously shown that this sensitivity could be discriminated from that seen in ataxia-telangiectasia (A-T). The cellular response to ultraviolet radiation below 280 nm (UVC) was characteristic of XP cells, indicating the second instance, in our experience, of dual cellular UVC and ionizing radiation hypersensitivity in XP. We then set out to evaluate any defects in repair of ionizing radiation damage and to verify any direct contribution of the XPC gene. The cells were defective in repair of a fraction of double strand breaks, with a pattern reminiscent of A-T. The cell line was immortalized with the vector pSV3neo and the XPC cDNA transfected in to correct the defect. The progeny derived from this transfection showed the presence of the XPC gene product, as measured by immunoblotting. A considerable restoration of normal UVC, but not ionizing radiation, sensitivity was observed amongst the clones. This differential correction of cellular sensitivity is strong evidence for the presence of a defective radiosensitivity gene, distinct from XPC, which is responsible for the clinical hypersensitivity to ionizing radiation. It is important to resolve how widespread ionizing radiation sensitivity is amongst XP patients.