Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Johansson, Lennart
Publications (10 of 53) Show all publications
Johansson, L. & Andersson, M. (2022). Diagnostic dosimetry. In: Michael Ljungberg (Ed.), Handbook of nuclear medicine and molecular imaging for physicists: modelling, dosimetry and radiation protection, volume ii (pp. 33-68). CRC Press
Open this publication in new window or tab >>Diagnostic dosimetry
2022 (English)In: Handbook of nuclear medicine and molecular imaging for physicists: modelling, dosimetry and radiation protection, volume ii / [ed] Michael Ljungberg, CRC Press, 2022, p. 33-68Chapter in book (Refereed)
Abstract [en]

Diagnostic nuclear medicine, more recently also named functional molecular imaging, deals with medical procedures performed to help diagnose a variety of diseases. The procedures are based on the use of tracer amounts of radioactive material, where a radionuclide is attached to a ligand with specific affinity to a physiological, metabolic, or receptor-specific process. To balance the benefit of a procedure, the calculation of the mean absorbed dose in organs and tissues for representative groups of patients is one important parameter in the justification of the diagnostic procedure. This also applies to the use of radiopharmaceuticals to volunteers in clinical research. Specific biokinetic models are created to describes the uptake, turn-over and retention in the human body. Together with mathematically describable anatomical models, representing groups of patients, these are used to estimate the mean absorbed dose in organs and tissues. This facilitate the estimations of the quantity effective dose, which is a dose quantity to estimate the risk to later in life develop a radiation-induced cancer for a group of reference patients. The chapter describes methods for diagnostic internal dosimetry, assessment of biokinetic data for individual patients/volunteers as well as construction of biokinetic and dosimetric models for representative groups of patients.

Place, publisher, year, edition, pages
CRC Press, 2022
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-200862 (URN)10.1201/9780429489549-3 (DOI)2-s2.0-85140659631 (Scopus ID)9780429952227 (ISBN)9781138593299 (ISBN)
Available from: 2022-11-10 Created: 2022-11-10 Last updated: 2022-11-10Bibliographically approved
Sandgren, K., Johansson, L., Axelsson, J., Jonsson, J., Ögren, M., Ögren, M., . . . Widmark, A. (2019). Radiation dosimetry of [Ga-68]PSMA-11 in low-risk prostate cancer patients. EJNMMI Physics, 6, Article ID 2.
Open this publication in new window or tab >>Radiation dosimetry of [Ga-68]PSMA-11 in low-risk prostate cancer patients
Show others...
2019 (English)In: EJNMMI Physics, E-ISSN 2197-7364, Vol. 6, article id 2Article in journal (Refereed) Published
Abstract [en]

Background: 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients.

Methods: Six low-risk prostate cancer patients were injected with 133–178 MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255 min post-injection. Urine was collected up to 4 h post-injection, and venous blood samples were drawn at 45 min, 85 min, 175 min, and 245 min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods.

Results: [68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5 min (91%) and 4.4 h (9%). The effective dose was calculated to 0.022 mSv/MBq. The kidneys received approximately 40 mGy after an injection with 160 MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12 mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051 mGy/MBq).

Conclusion: The effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Radiation dosimetry, [Ga-68]PSMA-11, PSMA, PET-tracer, Prostate cancer, Absorbed dose and effective dose, Glu-NH-CO-NH-Lys(Ahx)-HBED-CC
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-155760 (URN)10.1186/s40658-018-0239-2 (DOI)000455503100001 ()30631980 (PubMedID)2-s2.0-85060909369 (Scopus ID)
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2023-03-24Bibliographically approved
Lizana, H., Johansson, L., Axelsson, J., Larsson, A., Ögren, M., Linder, J., . . . Jakobson Mo, S. (2018). Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects. Journal of Nuclear Medicine, 59(8), 1275-1280
Open this publication in new window or tab >>Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects
Show others...
2018 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 59, no 8, p. 1275-1280Article in journal (Refereed) Published
Abstract [en]

F-18-(E)-N-(3-iodoprop-2-enyl)-2 beta-carbofluoroethoxy-3 beta-(4'-methylphenyl) nortropane (F-18-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-18-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of F-18-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 mu Gy/MBq), followed by the liver (46 mu Gy/MBq). The effective dose was 23 mu Sv/MBq (range, 19-28 mu Sv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that F-18-FE-PE2I is a suitable radioligand for DAT imaging.

Keywords
F-18-FE-PE2I, dosimetry, biodistribution, DAT, effective dose
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-150823 (URN)10.2967/jnumed.117.197186 (DOI)000440582000020 ()29348315 (PubMedID)2-s2.0-85051260875 (Scopus ID)
Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2023-03-23Bibliographically approved
Andersson, M., Mattsson, S., Johansson, L. & Leide-Svegborn, S. (2017). A biokinetic and dosimetric model for ionic indium in humans. Physics in Medicine and Biology, 62(16), 6397-6407
Open this publication in new window or tab >>A biokinetic and dosimetric model for ionic indium in humans
2017 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 16, p. 6397-6407Article in journal (Refereed) Published
Abstract [en]

This paper reviews biokinetic data for ionic indium, and proposes a biokinetic model for systemic indium in adult humans. The development of parameter values focuses on human data and indium in the form of ionic indium(III), as indium chloride and indium arsenide. The model presented for systemic indium is defined by five different pools: plasma, bone marrow, liver, kidneys and other soft tissues. The model is based on two subsystems: one corresponding to indium bound to transferrin and one where indium is transported back to the plasma, binds to red blood cell transferrin and is then excreted through the kidneys to the urinary bladder. Absorbed doses to several organs and the effective dose are calculated for In-111- and In-113m-ions. The proposed biokinetic model is compared with previously published biokinetic indium models published by the ICRP. The absorbed doses are calculated using the ICRP/ICRU adult reference phantoms and the effective dose is estimated according to ICRP Publication 103. The effective doses for In-111 and In-113m are 0.25 mSv MBq(-1) and 0.013 mSv MBq(-1) respectively. The updated biokinetic and dosimetric models presented in this paper take into account human data and new animal data, which represent more detailed and presumably more accurate dosimetric data than that underlying previous models for indium.

Place, publisher, year, edition, pages
Institute of Physics Publishing (IOPP), 2017
Keywords
biokinetic model, indium, absorbed dsoe, effective dose
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:umu:diva-145625 (URN)10.1088/1361-6560/aa779f (DOI)000425825900003 ()28726676 (PubMedID)2-s2.0-85026788703 (Scopus ID)
Available from: 2018-03-15 Created: 2018-03-15 Last updated: 2023-03-23Bibliographically approved
Andersson, M., Johansson, L., Eckerman, K. & Mattsson, S. (2017). IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms. EJNMMI Research, 7, Article ID 88.
Open this publication in new window or tab >>IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms
2017 (English)In: EJNMMI Research, E-ISSN 2191-219X, Vol. 7, article id 88Article in journal (Refereed) Published
Abstract [en]

Background: To date, the estimated radiation-absorbed dose to organs and tissues in patients undergoing diagnostic examinations in nuclear medicine is derived via calculations based on models of the human body and the biokinetic behaviour of the radiopharmaceutical. An internal dosimetry computer program, IDAC-Dose2.1, was developed based on the International Commission on Radiological Protection (ICRP)-specific absorbed fractions and computational framework of internal dose assessment given for reference adults in ICRP Publication 133. The program uses the radionuclide decay database of ICRP Publication 107 and considers 83 different source regions irradiating 47 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of radionuclides. IDAC-Dose2.1 has a sub-module for absorbed dose calculations in spherical structures of different volumes and composition; this sub-module is intended for absorbed dose estimates in radiopharmaceutical therapy. For nine specific alpha emitters, the absorbed dose contribution from their decay products is also included in the committed absorbed dose calculations. Results: The absorbed doses and effective dose of I-131-iodide determined by IDAC-Dose2.1 were validated against the dosimetry program DCAL, showing identical results. IDAC-Dose2.1 was used to calculate absorbed doses for intravenously administered F-18-FDG and orally administered Tc-99m-pertechnetate and I-131-iodide, three frequently used radiopharmaceuticals. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated to be 0.016 mSv/MBq for F-18-FDG, 0.014 mSv/MBq for Tc-99m-pertechnetate, and 16 mSv/MBq for I-131-iodide. Conclusions: The internal dosimetry program IDAC-Dose2.1 was developed and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for diagnostic nuclear medicine using specific absorbed fraction values of the ICRP computational voxel phantoms. The sub-module for absorbed dose calculations in spherical structures 1 mm to 9 cm in diameter and different tissue composition was included to broaden the clinical usefulness of the program. The IDAC-Dose2.1 program is free software for research and available for download at http://www.idac-dose.org.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2017
Keywords
Internal dosimetry, ICRP, IDAC, DCAL, Effective dose, Radiopharmaceuticals, Diagnostic nuclear dicine
National Category
Radiology, Nuclear Medicine and Medical Imaging Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-141966 (URN)10.1186/s13550-017-0339-3 (DOI)000414462200001 ()29098485 (PubMedID)2-s2.0-85033236572 (Scopus ID)
Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2023-03-23Bibliographically approved
Leide-Svegborn, S., Ahlgren, L., Johansson, L. & Mattsson, S. (2016). Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption. European Journal of Nuclear Medicine and Molecular Imaging, 43(5), 808-821
Open this publication in new window or tab >>Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption
2016 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 5, p. 808-821Article in journal (Refereed) Published
Abstract [en]

Purpose To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data.

Methods Activity concentrations in breast milk from 53 breastfeeding patients were determined. The milk was collected at various times after administration of 16 different radiopharmaceuticals. The fraction of the activity administered to the mother excreted in the breast milk, the absorbed doses to various organs and tissues and the effective dose to the infant were estimated.

Results The fraction of the administered activity excreted per millilitre of milk varied widely from 10(-10) to 10(-3) MBq/MBq administered. For Tc-99m-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for Tc-99m-labelled red blood cells (RBC) to 19 % for Tc-99m-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7 x 10(-6) mSv/MBq for Tc-99m-labelled RBC to 3.6 x 10(-2) mSv/MBq for Tc-99m-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % (Cr-51-EDTA) to 48 % (I-131-NaI). The effective dose ranged from 5.6 x 10(-5) mSv(infant)/MBq(mother) (Cr-51-EDTA) to 106 mSv(infant)/MBq(mother) (I-131-NaI).

Conclusions Based on an effective dose limit of 1 mSv to the infant and a typical administered activity, we recommend cessation of breastfeeding for I-131-NaI and interruption of feeding for 12 h for I-125-iodohippurate, I-131-iodohippurate, Tc-99m-pertechnetate and Tc-99m-MAA. During this 12-h period all breast milk should be expressed at least three times and discarded. For the other radiopharmaceuticals included in this study, no interruption of breastfeeding is necessary.

Keywords
Absorbed dose, Breastfeeding, Breast milk, Nuclear medicine, Radiopharmaceutical
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-120610 (URN)10.1007/s00259-015-3286-0 (DOI)000373306800002 ()26732471 (PubMedID)2-s2.0-84953337983 (Scopus ID)
Available from: 2016-08-10 Created: 2016-05-18 Last updated: 2023-03-24Bibliographically approved
Andersson, M., Johansson, L., Mattsson, S., Minarik, D. & Leide-Svegborn, S. (2016). Organ doses and effective dose for five pet radiopharmaceuticals. Radiation Protection Dosimetry, 169(1-4), 253-258
Open this publication in new window or tab >>Organ doses and effective dose for five pet radiopharmaceuticals
Show others...
2016 (English)In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 169, no 1-4, p. 253-258Article in journal (Refereed) Published
Abstract [en]

Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by 18F-fluorodeoxyglucose (18F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are 18F-fluoride, 18F-fluoroethyltyrosine (18F-FET), 18F-deoxyfluorothymidine (18F-FLT), 18F-fluorocholine (18F-choline) and 11C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for 18F-fluoride. The estimated effective dose in mSv MBq−1 was 1.5E−02 for 18F-FET, 1.5E−02 for 18F-FLT, 2.0E−02 for 18F-choline, 9.0E−03 for 18F-fluoride and 4.4E−03 for 11C-raclopride.

Place, publisher, year, edition, pages
Oxford University Press, 2016
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-126764 (URN)10.1093/rpd/ncw033 (DOI)000383492100039 ()26977075 (PubMedID)2-s2.0-84979055642 (Scopus ID)
Available from: 2016-10-18 Created: 2016-10-13 Last updated: 2023-03-24Bibliographically approved
Häggström, I., Axelsson, J., Schmidtlein, R., Karlsson, M., Garpebring, A., Johansson, L., . . . Larsson, A. (2015). A Monte Carlo study of the dependence of early frame sampling on uncertainty and bias in pharmacokinetic parameters from dynamic PET. Journal of Nuclear Medicine Technology, 43(1), 53-60
Open this publication in new window or tab >>A Monte Carlo study of the dependence of early frame sampling on uncertainty and bias in pharmacokinetic parameters from dynamic PET
Show others...
2015 (English)In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, Vol. 43, no 1, p. 53-60Article in journal (Refereed) Published
Abstract [en]

Compartmental modeling of dynamic PET data enables quantifi- cation of tracer kinetics in vivo, through the calculated model parameters. In this study, we aimed to investigate the effect of early frame sampling and reconstruction method on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias and uncertainty (SD). Methods: The GATE Monte Carlo software was used to simulate 2 · 15 dynamic 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) brain PET studies, typical in terms of noise level and kinetic parameters. The data were reconstructed by both 3- dimensional (3D) filtered backprojection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6 dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15 s. Bias and SD were evaluated for fitted parameter estimates, calculated from regions of interest. Results: The 2-tissue-model parameter estimates K1, k2, and fraction of arterial blood in tissue depended on early frame sampling, and a sampling of 6–15 s generally minimized bias and SD. The shortest sampling of 1 s yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM, respectively, and a parameter uncertainty that was 10%–70% higher. The schemes from 4 to 15 s were generally not significantly different in regards to bias and SD. Typically, the reconstruction method 3DRP yielded less framesampling dependence and less uncertain results, compared with OSEM, but was on average more biased. Conclusion: Of the 6 sampling schemes investigated in this study, an early frame duration of 6–15 s generally kept both bias and uncertainty to a minimum, for both 3DRP and OSEM reconstructions. Veryshort frames of 1 s should be avoided because they typically resulted in the largest parameter bias and uncertainty. Furthermore, 3DRP may be p

Keywords
dynamic PET, Monte Carlo; GATE, compartment modeling, frame sampling
National Category
Other Physics Topics Medical Image Processing
Research subject
radiation physics
Identifiers
urn:nbn:se:umu:diva-95128 (URN)10.2967/jnmt.114.141754 (DOI)2-s2.0-84930354810 (Scopus ID)
Funder
Swedish National Infrastructure for Computing (SNIC), HPC2N-2009-001
Available from: 2014-10-22 Created: 2014-10-22 Last updated: 2023-09-14Bibliographically approved
Hedman, A., Gogani, J. B., Granström, M., Johansson, L., Andersson, J. S. & Ramebäck, H. (2015). Characterization of HPGe detectors using Computed Tomography. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 785(11 June 2015), 21-25
Open this publication in new window or tab >>Characterization of HPGe detectors using Computed Tomography
Show others...
2015 (English)In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, ISSN 0168-9002, E-ISSN 1872-9576, Vol. 785, no 11 June 2015, p. 21-25Article in journal (Refereed) Published
Abstract [en]

Computed Tomography (CT) high resolution imaging have been used to investigate if there is a significant change in the crystal-to-window distance, i.e. the air gap thickness, in a small n-type detector cooled to 77 K, and in a medium sized p-type HPGe detector when cooled to 100 K. The findings were compared to detector dimension data made available by the manufacturer. The air gap thickness increased by (0.38 +/- 0.07) mm for the n-type detector and by (0.40 +/- 0.15) mm for the p-type detector when the detectors were cooled to 77 resp. 100 K compared to at room temperature. Monte Carlo calculations indicate that these differences have a significant impact on the efficiency in close geometries (< 5 cm). In the energy range of 40-700 keV with a source placed directly on endcap, the change in detector efficiency with temperature is 1.9-2.9% for the n-type detector and 0.3-2.1% for the p-type detector. The measured air gap thickness when cooling the detector was 1.1 mm thicker than manufacturer data for the n-type detector and 0.2 mm thicker for the p-type detector. In the energy range of 40-700 keV and with a source on endcap, this result in a change in detector efficiency of 5.2-7.1% for the n-type detector and 0.2-1.0% for the p-type detector, Le the detector efficiency is overestimated using data available by the manufacturer. (C) 2015 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Gamma spectrometry, HPGe, Computed Tomography, Monte Carlo modelling, Gespecor, Semi-empirical calibration
National Category
Medical Image Processing
Identifiers
urn:nbn:se:umu:diva-103122 (URN)10.1016/j.nima.2015.02.041 (DOI)000352815400005 ()2-s2.0-84924955987 (Scopus ID)
Available from: 2015-05-26 Created: 2015-05-18 Last updated: 2023-03-23Bibliographically approved
Lindgren, T., Stigbrand, T., Råberg, A., Riklund, K., Johansson, L. & Eriksson, D. (2015). Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT116 p53 +/+ and HCT116 p53 -/- colorectal carcinoma cell lines. International Journal of Radiation Biology, 91(1), 99-111
Open this publication in new window or tab >>Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT116 p53 +/+ and HCT116 p53 -/- colorectal carcinoma cell lines
Show others...
2015 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 91, no 1, p. 99-111Article in journal (Refereed) Published
Abstract [en]

Purpose : To study the kinetics of gene expression alterations following radiation exposure of isogenic HCT116 p53+/+ and HCT116 p53-/- cell lines. Materials and methods : Cells were exposed to 5 Gy of irradiation (Cs-137) and genome-wide temporal expression analysis using Illumina bead chip arrays was performed. Signalling pathways were explored using Metacore (Genego). Biological responses including cell cycle checkpoint activation, centrosome amplification and senescence induction were analyzed. Results : Significant differences in the radiation response were observed between the p53+/+ and the p53-/- cell lines. In p53+/+ cells concurrent G1- and G2-arrests were activated followed by senescence induction. Increased expression of genes associated with senescence, senescence associated secretory phenotype (SASP) and repression of genes essential for G2-M transition were detected. P53-/- cells arrested mainly in G2 followed by centrosome amplification, mitotic slippage and a subsequent increase of polyploid cells. Furthermore, changes in expression correlated well with these signs of mitotic catastrophe. Conclusions : The presence or absence of p53 triggers different signalling cascades with different endpoints. Elucidating these differences is important as it enables improvement of radiation treatment and could be used to develop new combination treatments with specific inhibitors of key regulators of these cell death modalities.

Keywords
radiation, gene expression, senescence, p53, mitotic catastrophe, cell cycle checkpoint
National Category
Cell and Molecular Biology
Research subject
Immunology; radiation physics
Identifiers
urn:nbn:se:umu:diva-80231 (URN)10.3109/09553002.2015.959668 (DOI)000349557900011 ()25219679 (PubMedID)2-s2.0-84923069955 (Scopus ID)
Note

Originally published in manuscript form.

Available from: 2013-09-12 Created: 2013-09-12 Last updated: 2023-03-24Bibliographically approved
Organisations

Search in DiVA

Show all publications