To study radioresistance in esophageal adenocarcinoma, we generated an isogenic cell line model by exposing OE33 esophageal adenocarcinoma cells to clinically relevant fractionated doses of radiation (cumulative dose 50 Gy). A clonogenic assay confirmed enhanced survival of the radioresistant OE33 subline (OE33 R). To our knowledge, we are the first to generate an isogenic model of radioresistance in esophageal adenocarcinoma. This model system was characterized in terms of growth, cell cycle distribution and checkpoint operation, apoptosis, reactive oxygen species generation and scavenging, and DNA damage. While similar properties were found for both the parental OE33 (OE33 P) cells and radioresistant OE33 R cells, OE33 R cells demonstrated greater repair of radiation-induced DNA damage. Our results suggest that the radioresistance of OE33 R cells is due at least in part to increased DNA repair.
Niamh Lynam-Lennon, John V Reynolds, Graham P Pidgeon, Joanne Lysaght, Laure Marignol, and Stephen G Maher
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Recognition of O6MeG lesions by MGMT and mismatch repair proficiency may be a prerequisite for low-dose radiation hypersensitivity.
Low-dose hyper-radiosensitivity (HRS) is the phenomenon whereby cells exposed to radiation doses of less than ∼0.5 Gy exhibit increased cell killing relative to that predicted from back-extrapolating high-dose survival data using a linear-quadratic model. While the exact mechanism remains to be elucidated, the involvement of several molecular repair pathways has been documented. These processes in turn are also associated with the response of cells to O6-methylguanine (O6MeG) lesions. We propose a model in which the level of low-dose cell killing is determined by the efficiency of both pre-replicative repair by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT) and post-replicative repair by the DNA mismatch repair (MMR) system. We therefore hypothesized that the response of cells to low doses of radiation is dependent on the expression status of MGMT and MMR proteins. MMR (MSH2, MSH6, MLH1, PMS1, PMS2) and MGMT protein expression signatures were determined in a panel of normal (PWR1E, RWPE1) and malignant (22RV1, DU145, PC3) prostate cell lines and correlated with clonogenic survival and cell cycle analysis. PC3 and RWPE1 cells (HRS positive) were associated with MGMT and MMR proficiency, whereas HRS negative cell lines lacked expression of at least one (MGMT or MMR) protein. MGMT inactivation had no significant effect on cell survival. These results indicate a possible role for MMR-dependent processing of damage produced by low doses of radiation.
Lynn Martin, Brian Marples, Mary Coffey, Mark Lawler, Donal Hollywood, and Laure Marignol
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Courtship raises male fertilization success through post-mating sexual selection in a spider.
Courtship is well known for its positive effects on mating success. However, in polyandrous species, sexual selection continues to operate after copulation. Cryptic female choice is expected under unpredictable mating rates in combination with sequential mate encounters. However, there are very few accounts of the effects of courtship on cryptic female choice, and the available evidence is often correlative.
Mature Argiope bruennichi females are always receptive and never attack or reject males before mating, although sexual cannibalism after mating occurs regularly. Still, males usually perform an energetic vibratory display prior to copulation. We tested the hypothesis that beneficial effects of courtship arise cryptically, during or after mating, resulting in increased paternity success under polyandry. Manipulating courtship duration experimentally, we found that males that mated without display had a reduced paternity share even though no differences in post-copulatory cannibalism or copulation duration were detected. This suggests that the paternity advantage associated with courtship arose through female-mediated processes after intromission, meeting the definition of cryptic female choice.
Jutta M Schneider and Kristiani Lesmono
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Hypoxia response element-driven cytosine deaminase/5-fluorocytosine gene therapy system: a highly effective approach to overcome the dynamics of tumour hypoxia and enhance the radiosensitivity of prostate cancer cells in vitro.
We proposed to exploit hypoxia-inducible factor (HIF)-1alpha overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF-1alpha to arrangements of hypoxia response elements. CD is a prodrug activation enzyme, which converts inactive 5-fluorocytosine to active 5-fluorouracil (5-FU), allowing selective killing of vector containing cells.
Laure Marignol, Ruth Foley, Thomas Southgate, Mary Coffey, Donal Hollywood and Mark Lawler
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Addendum to the IPEMB code of practice for the determination of absorbed dose for x-rays below 300 kV generating potential (0.035 mm Al–4 mm Cu HVL)
This addendum to the code of practice for the determination of absorbed dose for x-rays below 300 kV has recently been approved by the IPEM and introduces three main changes: (i) Due to a lack of available data the original code recommended a value of unity for kch in the very-low-energy range (0.035–1.0 mm Al HVL). A single table of kch values, ranging from 1.01 to 1.07, applicable to both designated chamber types is now presented. (ii) For medium-energy x-rays (0.5–4 mm Cu HVL) methods are given to determine the absorbed dose to water either at 2 cm depth or at the surface of a phantom depending on clinical needs. Determination of the dose at the phantom surface is derived from an in-air measurement and by extending the low-energy range up to 4 mm Cu HVL. Relevant backscatter factors and ratios of mass energy absorption coefficients are given in the addendum. (iii) Relative dosimetry: although not normally forming part of a dosimetry code of practice a brief review of the current literature on this topic has been added as an appendix. This encompasses advice on techniques for measuring depth doses, applicator factors for small field sizes, dose fall off with increasing SSD and choice of appropriate phantom materials and ionization chambers.
R J Aukett, J E Burns, A G Greener, R M Harrison, C Moretti, A E Nahum and K E Rosser
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The IPEMB code of practice for the determination of absorbed dose for x-rays below 300 kV generating potential (0.035 mm Al – 4 mm Cu HVL; 10 – 300 kV generating potential)
This new code of practice for the determination of absorbed dose for x-rays below 300 kV has recently been approved by the IPEMB and introduces the following changes to the previous codes: (i) The determination of absorbed dose is based on the air kerma determination (exposure measurement) method. (ii) An air kerma calibration factor for the ionization chamber is used. (iii) The use of the F (rad/röentgen) conversion factor is abandoned and replaced by the ratio of the mass – energy absorption coefficients of water and air for converting absorbed dose to air to absorbed dose to water. New values for ratios of these coefficients are recommended. Perturbation and other correction factors are incorporated in the equations. (iv) New backscatter factors are recommended. (v) Three separate energy ranges are defined, with specific procedures for each range. These ranges are: (a) 0.5 to 4 mm Cu HVL; for this range calibration at 2 cm depth in water with a thimble ion chamber is recommended. (b) 1.0 to 8.0 mm Al HVL; for this range calibration in air with a cylindrical ion chamber and the use of tabulated values of the backscatter factor are recommended. (c) 0.035 to 1.0 mm Al HVL; for this range calibration on the surface of a phantom with a parallel-plate ionization chamber is recommended.
S C Klevenhagen, R J Aukett, R M Harrison, C Moretti, A E Nahum and K E Rosser
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AAPM protocol for 40–300 kV x-ray beam dosimetry in radiotherapy and radiobiology
The American Association of Physicists in Medicine (AAPM) presents a new protocol, developed by the Radiation Therapy Committee Task Group 61, for reference dosimetry of low- and medium-energy x rays for radiotherapy and radiobiology math formula It is based on ionization chambers calibrated in air in terms of air kerma. If the point of interest is at or close to the surface, one unified approach over the entire energy range shall be used to determine absorbed dose to water at the surface of a water phantom based on an in-air measurement (the “in-air” method). If the point of interest is at a depth, an in-water measurement at a depth of 2 cm shall be used for tube potentials ⩾100 kV (the “in-phantom” method). The in-phantom method is not recommended for tube potentials <100 kV. Guidelines are provided to determine the dose at other points in water and the dose at the surface of other biological materials of interest. The protocol is based on an up-to-date data set of basic dosimetry parameters, which produce consistent dose values for the two methods recommended. Estimates of uncertainties on the final dose values are also presented.
C M Ma, C W Coffey, L A DeWerd, C Liu, R Nath, S M Seltzer & J P Seuntjens
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Late Irradiation Damage to the Skin Caused by Soft X-ray Radiation Therapy of Cutaneous Tumours
BACKGROUND: Although radiotherapy of skin tumors has lost its former preeminence, there is still need for this modality. The aim of this study was, therefore, to determine the frequency of radiogenic ulcers and tumors following soft x-ray therapy of skin lesions....