ORCID Profile
0000-0003-2324-4748
Current Organisations
University of Adelaide
,
Flinders University
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Nuclear physics | Nuclear and plasma physics | Law and society and socio-legal research | Mineral Processing/Beneficiation | Resources Engineering and Extractive Metallurgy | Inorganic Geochemistry | Mineral processing/beneficiation | Lasers and Quantum Electronics |
Environmentally Sustainable Mineral Resource Activities not elsewhere classified | Concentrating Processes of Base Metal Ores (excl. Aluminium and Iron Ores) | Mining and Extraction of Copper Ores |
Publisher: SAGE Publications
Date: 10-2006
DOI: 10.2203/DOSE-RESPONSE.06-004.SYKES
Abstract: Almost all of our knowledge about the mutational effect of radiation has come from high dose studies which are generally not relevant to public exposure. The pKZ1 mouse recombination mutagenesis assay enables study of the mutational effect of very low doses of low LET radiation (μGy to cGy range) in a whole animal model. The mutational end-point studied is chromosomal inversion which is a common mutation in cancer. We have observed 1) a non-linear dose response of induced inversions in pKZ1 mice exposed to a wide dose range of low LET radiation, 2) the ability of low priming doses to cause an adaptive response to subsequent higher test doses and 3) the effect of genetic susceptibility where animals that are heterozygous for the Ataxia Telangiectasia gene (Atm) exhibit different responses to low dose radiation compared to their normal litter-mates.
Publisher: Wiley
Date: 2001
DOI: 10.1002/EM.1013
Publisher: Wiley
Date: 2003
DOI: 10.1002/EM.1014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
DOI: 10.1097/HP.0000000000000810
Abstract: Ionizing radiation exposure to the lens of the eye is a known cause of cataractogenesis. Historically, it was believed that the acute threshold dose for cataract formation was 5 Sv, and annual dose limits to the lens were set at 150 mSv. Recently, however, the International Commission on Radiological Protection has reduced their threshold dose estimate for deterministic effects to 0.5 Gy and is now recommending an occupational limit of 20 mSv per year on average. A number of organizations have questioned whether this new threshold and dose limit are justified based on the limited reliable data concerning radiation-induced cataracts. This review summarizes all of the published human epidemiological data on ionizing radiation exposure to the lens of the eye in order to evaluate the proposed threshold. Data from a variety of exposure cohorts are reviewed, including atomic bomb survivors, Chernobyl liquidators, medical workers, and radiotherapy patients. Overall, there is not conclusive evidence that the threshold dose for cataract formation should be reduced to 0.5 Gy. Many of the studies reviewed here are challenging to incorporate into an overall risk model due to inconsistencies with dosimetry, s le size, and scoring metrics. Additionally, risk levels in the studied cohorts may not relate to occupational scenarios due to differences in dose rate, radiation quality, age at exposure and latency period. New studies should be designed specifically focused on occupational exposures, with reliable dosimetry and grading methods for lens opacities, to determine an appropriate level for dose threshold and exposure limit.
Publisher: Elsevier BV
Date: 02-1998
DOI: 10.1016/S0027-5107(97)00213-3
Abstract: Somatic intrachromosomal recombination (SICR) can result in chromosomal inversion and deletion, mechanisms which are important in carcinogenesis. We have utilised a transgenic mouse model to study SICR inversion events in spleen cells. The transgenic construct is designed so that expression of an Escherichia coli lacZ transgene only occurs in a cell when an SICR inversion event occurs in the region of the transgene. The inversion events can then be detected by histochemical staining of frozen spleen sections for transgene expression and by polymerase chain reaction across the inversion breakpoints. The spontaneous inversion frequency in spleen rose 2-fold from 1.54 +/- 0.24 x 10(-4) (mean +/- SE) in 4-month-old transgenic mice to 3.12 +/- 0.67 x 10(-4) in 22-month-old mice. Four- or 8-month-old mice were treated with a single intraperitoneal injection of cyclophosphamide, with doses ranging from 0.01 to 100 mg/kg. The animals were killed 3 days after treatment. A significant induction of SICR inversions was detected at all doses with a 3.2-fold maximum induction of inversions detected at 10 mg/kg. These results suggest that the transgenic mouse model used here may be a sensitive model for studying the role of SICR in mutation and in studying risk assessment of environmental DNA-damaging agents.
Publisher: Elsevier BV
Date: 03-2002
DOI: 10.1016/S0027-5107(02)00007-6
Abstract: Chromosomal inversions and deletions can occur via somatic intrachromosomal recombination (SICR), a mechanism known to be important in mutagenesis and carcinogenesis. Here, we demonstrate a dose-dependent increase or decrease in SICR inversion frequency both in vivo and in vitro after treatment with etoposide, using the pKZ1 mouse mutagenesis model. pKZ1 mice received a single intraperitoneal injection of etoposide dose ranging from 0.0005 to 50mg/kg. Animals were sacrificed 3 days after treatment and the spleen was analysed for SICR. A significant 1.4-3.1-fold induction of SICR inversion events was detected in pKZ1 mice after treatment with etoposide doses ranging from 0.05 to 50 mg/kg etoposide. However, inversion frequencies after treatment with 0.0005 and 0.005 mg/kg etoposide decreased significantly to 0.67 and 0.43 of the levels observed in control animals, respectively. A pKZ1 mouse hybridoma cell line was exposed to etoposide (1-1000 nM) and a similar pattern of SICR response to that detected in vivo was observed. A significant 2.3-4.6-fold induction of SICR inversions was observed in pKZ1 cells treated with 100 and 1000 nM etoposide. Inversion frequencies after treatment with 1 and 10nM etoposide decreased significantly to 0.31 and 0.5 of the level observed in control cell lines. Our in vitro studies complement our in vivo studies and exclude a kinetic phenomenon as the responsible mechanism of reduction in SICR in response to low dose etoposide. Determination of the exact mechanism and significance of recombination suppression at low doses of etoposide treatment requires further investigation.
Publisher: Radiation Research Society
Date: 10-2004
DOI: 10.1667/RR3228
Abstract: Almost all of the data on the biological effects of ionizing radiation come from studies of high doses. However, the human population is unlikely to be exposed to such doses. Regulatory limits for radiation exposure are based on the linear no-threshold model, which predicts that the relationship between biological effects and radiation dose is linear, and that any dose has some effect. Chromosomal changes are an important effect of ionizing radiation because of their role in carcinogenesis. Here we exposed pKZ1 mice to single whole-body X-radiation doses as low as 1 microGy. We observed three different phases of response: (1) an induction of inversions at ultra-low doses, (2) a reduction below endogenous inversion frequency at low doses, and (3) an induction of inversions again at higher doses. These results do not fit a linear no-threshold model, and they may have implications for the way in which regulatory standards are presently set and for understanding radiation effects.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/09553000701420582
Abstract: To investigate the effect of being heterozygous for a knockout mutation in the ataxia telangiectasia (Atm) gene on radiation adaptive response. DNA recombination, as measured by pKZ1 inversion frequency, was quantified by histochemistry in Atm knockout heterozygous prostate and spleen 3 days after treatment with a priming dose of 0.01 or 10 mGy X-radiation 4 h prior to a challenge dose of 1,000 mGy. In spleen and prostate, a single dose of 0.01 mGy caused an induction in inversion frequency but a dose of 10 mGy prevented the induction of a proportion of endogenous inversions. Both doses induced an adaptive response, of similar magnitude, to a subsequent high challenge dose for chromosomal inversions in both spleen and prostate. The adaptive response completely prevented the induction of inversions from a 1,000 mGy challenge dose and also a proportion of endogenous inversions. The adaptive responses and distribution of inversions across gland cross-sections observed here in Atm knockout heterozygote prostate were similar to those induced in Atm wild-type prostate in a previous study. Being heterozygous for a knockout mutation in the Atm gene does not affect the endogenous pKZ1 inversion frequency, the inversion response to single low radiation doses used here, or the induction of a radiation adaptive response for inversions in pKZ1 mouse spleen or prostate.
Publisher: Elsevier BV
Date: 04-06-2004
Publisher: Elsevier BV
Date: 06-1999
Publisher: Radiation Research Society
Date: 11-2006
DOI: 10.1667/RR0689.1
Publisher: Society of Economic Geologists
Date: 22-02-2016
Publisher: Radiation Research Society
Date: 11-2001
DOI: 10.1667/0033-7587(2001)156[0495:EOETMR]2.0.CO;2
Abstract: Radiofrequency (RF) radiation emitted from mobile phones is not considered to be directly genotoxic, but it may have downstream effects on cellular DNA. We studied the effect of 4 W/kg pulsed 900 MHz RF radiation on somatic intrachromosomal recombination in the spleen in the pKZ1 recombination mutagenesis model. Somatic intrachromosomal recombination inversion events were detected in spleen tissue of pKZ1 mice by histochemical staining for E. coli beta-galactosidase protein in cells in which the lacZ transgene has undergone an inversion event. pKZ1 mice were exposed daily for 30 min to plane-wave fields of 900 MHz with a pulse repetition frequency of 217 Hz and a pulse width of 0.6 ms for 1, 5 or 25 days. Three days after the last exposure, spleen sections were screened for DNA inversion events. There was no significant difference between the control and treated groups in the 1- and 5-day exposure groups, but there was a significant reduction in inversions below the spontaneous frequency in the 25-day exposure group. This observation suggests that exposure to RF radiation can lead to a perturbation in recombination frequency which may have implications for recombination repair of DNA. The biological significance of a reduction below the spontaneous frequency is not known. The number of mice in each treatment group in this study was small (n = 10 or n = 20). Therefore, repetition of this study with a larger number of animals is required to confirm these observations.
Publisher: Springer Science and Business Media LLC
Date: 09-2011
Publisher: Informa UK Limited
Date: 12-06-2019
Publisher: Inderscience Publishers
Date: 2009
Publisher: Wiley
Date: 2006
DOI: 10.1002/EM.20238
Publisher: Elsevier BV
Date: 09-2005
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.MRFMMM.2006.08.002
Abstract: Somatic intrachromosomal recombination can result in inversions and deletions in DNA, which are important mutations in cancer. The pKZ1 chromosomal inversion assay is a sensitive assay for studying the effects of DNA damaging agents using chromosomal inversion as a mutation end-point. We have previously demonstrated that the chromosomal inversion response in pKZ1 spleen after single low doses of X-radiation exposure does not follow the linear no-threshold dose-response model. Here, we optimised a chromosomal inversion screening method to study the effect of low dose X-radiation exposure in pKZ1 prostatic tissue. In the present study, a significant induction in inversions was observed after ultra-low doses of 0.005-0.01 mGy or after a high dose of 1000 mGy, whereas a reduction in inversions to below the sham-treated frequency was observed between 1 and 10 mGy exposure. This is the first report of a reduction to below endogenous frequency for any mutation end-point in prostate. In addition, the doses of radiation studied were at least three orders of magnitude lower than have been reported in other mutation assays in prostate in vivo or in vitro. In sham-treated pKZ1 controls and in pKZ1 mice treated with low doses of 1-10 mGy the number of inversions/gland cross-section rarely exceeded three. Up to 4 and 7 inversions were observed in in idual prostatic gland cross-sections after doses < or =0.02 mGy and after 1000 mGy, respectively. The number of inversions identified in in idual cross-sections of prostatic glands of untreated mice and all treated mice other than the 1000 mGy treatment group followed a Poisson distribution. The dose-response curves and fold changes observed after all radiation doses studied were similar in spleen and prostate. These results suggest that the pKZ1 assay is measuring a fundamental response to DNA damage after low dose X-radiation exposure which is independent of tissue type.
Publisher: Wiley
Date: 2004
DOI: 10.1002/EM.20058
Publisher: Informa UK Limited
Date: 03-12-2021
Publisher: Radiation Research Society
Date: 06-2007
DOI: 10.1667/RR0764.1
Publisher: Elsevier BV
Date: 08-2002
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 05-2021
Publisher: Mineralogical Society of America
Date: 08-2015
DOI: 10.2138/AM-2015-5125
Location: Australia
Start Date: 06-2015
End Date: 06-2020
Amount: $2,526,617.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2023
End Date: 12-2027
Amount: $4,999,600.00
Funder: Australian Research Council
View Funded Activity