title: In vitro Effects of Selenium on DNA Damage in BRCA1 Cell Lines

authors: Mayall, Kirsty Rose

subjects: Selenium

abstract: Cancer of the breast is the most common cancer affecting women, with a 1 in 9 lifetime risk of developing breast cancer. Carriers of mutations in the breast cancer susceptibility gene, BRCA1, present with an increased lifetime risk of 80-95% of developing breast cancer. BRCA1 is a tumour-suppressor gene that is involved in DNA repair of double-strand breaks and transcriptional regulation.

Studies have shown that oral supplementation with Selenium (Se) could potentially be an effective preventive agent against BRCA1-mutation carriers. Se is an essential trace mineral that plays critical roles in maintaining health in humans. Se functions by protecting lipid membranes, proteins and DNA from free radical damage and is involved in redox regulation in the cell. These functions are mediated through specific Se-dependent proteins termed selenoproteins, in which Se is incorporated.

Se supplementation may exert its benefits by enhancing the DNA damage repair response. The effects also appear to be dependent on selenoprotein genotypes and concentration of Se in the body/diet. It is possible that Se supplementation may be effective in reducing the risk of breast cancer in BRCA1 carriers, but the use of organic Se compounds is likely to be preferable, but the dose-response needs to be determined.

The objectives of this research thesis are to evaluate the dose-response of sodium selenite and methylseleninic acid (MSA) in two BRCA1-mutated cancer cell lines in vitro. The MTT assay was used to monitor cell activity, along with the comet assay to evaluate the DNA damage level using a dose-response curve of the two Se compounds on control and bleomycin-induced DNA damaged cells. In addition, DNA from each cell line was sequenced to confirm the presence of the published BRCA1 mutation.

The data presented within this thesis demonstrates that a commonly-used inorganic form of Se, sodium selenite, is more genotoxic than the organic Se compound, MSA, in malignant BRCA1-mutated cells. Sodium selenite also has more direct cytotoxicity in BRCA1-mutated cells than MSA, as demonstrated by the MTT assay. However the enhanced repair capacity from Se on DNA damage in cells demonstrated by others has not been reproduced. Preliminary data showed potential at much lower doses (2 μM) of Se. Interestingly, the volatile metabolites produced from MSA appear to reduce DNA damage, supportive of this hypothesis. In order to understand if the effects observed are linked specifically to the BRCA1 mutation or breast cancer in general, future research should include the investigation of the effects of Se on breast cancer using alternative breast cancer cell lines, as well as non-malignant cells.

text: In vitro Effects of Selenium on DNA Damage in BRCA1 Cell Lines Cancer of the breast is the most common cancer affecting women, with a 1 in 9 lifetime risk of developing breast cancer. Carriers of mutations in the breast cancer susceptibility gene, BRCA1, present with an increased lifetime risk of 80-95% of developing breast cancer. BRCA1 is a tumour-suppressor gene that is involved in DNA repair of double-strand breaks and transcriptional regulation.

Studies have shown that oral supplementation with Selenium (Se) could potentially be an effective preventive agent against BRCA1-mutation carriers. Se is an essential trace mineral that plays critical roles in maintaining health in humans. Se functions by protecting lipid membranes, proteins and DNA from free radical damage and is involved in redox regulation in the cell. These functions are mediated through specific Se-dependent proteins termed selenoproteins, in which Se is incorporated.

Se supplementation may exert its benefits by enhancing the DNA damage repair response. The effects also appear to be dependent on selenoprotein genotypes and concentration of Se in the body/diet. It is possible that Se supplementation may be effective in reducing the risk of breast cancer in BRCA1 carriers, but the use of organic Se compounds is likely to be preferable, but the dose-response needs to be determined.

The objectives of this research thesis are to evaluate the dose-response of sodium selenite and methylseleninic acid (MSA) in two BRCA1-mutated cancer cell lines in vitro. The MTT assay was used to monitor cell activity, along with the comet assay to evaluate the DNA damage level using a dose-response curve of the two Se compounds on control and bleomycin-induced DNA damaged cells. In addition, DNA from each cell line was sequenced to confirm the presence of the published BRCA1 mutation.

The data presented within this thesis demonstrates that a commonly-used inorganic form of Se, sodium selenite, is more genotoxic than the organic Se compound, MSA, in malignant BRCA1-mutated cells. Sodium selenite also has more direct cytotoxicity in BRCA1-mutated cells than MSA, as demonstrated by the MTT assay. However the enhanced repair capacity from Se on DNA damage in cells demonstrated by others has not been reproduced. Preliminary data showed potential at much lower doses (2 μM) of Se. Interestingly, the volatile metabolites produced from MSA appear to reduce DNA damage, supportive of this hypothesis. In order to understand if the effects observed are linked specifically to the BRCA1 mutation or breast cancer in general, future research should include the investigation of the effects of Se on breast cancer using alternative breast cancer cell lines, as well as non-malignant cells.

year: 2015

title: Observations of wave energy fluxes and swash motions on a low-sloping, dissipative beach

authors: Guedes, Rafael M. C.

subjects: swash

abstract: Field observations of swash and ocean waves show that runup saturation at infragravity frequencies (<0.05 Hz) can occur under mild offshore energy conditions if the beach slope is sufficiently gentle. Infragravity saturation was observed for higher-frequency (>0.025–0.035 Hz) infragravity waves, where typically less than 5% of the (linear) energy flux was reflected from the beach and where, similar to the sea swell band, the swash energy was independent of offshore wave energy. The infragravity frequency range of saturation was determined by the tide, with saturation extending to lower frequencies at low tide when the local beach face slope over the concave-shaped profile was gentler. Runup was strongly dominated by infragravity frequencies, which accounted on average for 96% of the runup variance, and its energy levels were entirely consistent with strong infragravity wave dissipation observed in the surfzone, particularly when including the nonlinear contributions to the wave energy fluxes. The infragravity wave dissipation was strongly associated with breaking of sea swell waves, which abruptly decreased nonlinear transfers to infragravity frequencies and made infragravity dissipation prevail over forcing within the breaking region. Our observations show evidence of nonlinear interactions involving infragravity and high-frequency, harmonic waves and suggest that these harmonics could play a role in the wave energy balance near the shoreline on low-sloping, dissipative beaches.

text: Observations of wave energy fluxes and swash motions on a low-sloping, dissipative beach Field observations of swash and ocean waves show that runup saturation at infragravity frequencies (<0.05 Hz) can occur under mild offshore energy conditions if the beach slope is sufficiently gentle. Infragravity saturation was observed for higher-frequency (>0.025–0.035 Hz) infragravity waves, where typically less than 5% of the (linear) energy flux was reflected from the beach and where, similar to the sea swell band, the swash energy was independent of offshore wave energy. The infragravity frequency range of saturation was determined by the tide, with saturation extending to lower frequencies at low tide when the local beach face slope over the concave-shaped profile was gentler. Runup was strongly dominated by infragravity frequencies, which accounted on average for 96% of the runup variance, and its energy levels were entirely consistent with strong infragravity wave dissipation observed in the surfzone, particularly when including the nonlinear contributions to the wave energy fluxes. The infragravity wave dissipation was strongly associated with breaking of sea swell waves, which abruptly decreased nonlinear transfers to infragravity frequencies and made infragravity dissipation prevail over forcing within the breaking region. Our observations show evidence of nonlinear interactions involving infragravity and high-frequency, harmonic waves and suggest that these harmonics could play a role in the wave energy balance near the shoreline on low-sloping, dissipative beaches.

year: 2013-07

title: The embodied and lived experiences of welfare and care for highly impaired, high performance para-sport athletes in Aotearoa New Zealand

authors: Lowry, Amanda

abstract: Aligning with calls in critical disability studies to bring the body and impairment into disability sport, this thesis examines the welfare and care experiences of highly impaired athletes in high-performance sport. While a focus on athlete welfare has gained some international prominence, and a duty of care is increasingly invoked as an organisational and coaching responsibility, these developments remain largely disconnected from disability.  
The research is centred around two main objectives. First, to amplify the lived and embodied experiences of highly impaired, high performance disabled athletes as they prepare for, train, and compete in sport, and those who support them. Second, to understand how sporting institutions and regulations (within the broader context of government funding and national health care provision) influence welfare and care practices for high performance disabled athletes. 
Crip methodologies and Indigenous Māori storytelling methodologies such as pūrākau centres lived experience as a site of resistance and knowledge production. Using a reflexive, qualitative approach, including semi-structured interviews, autoethnographic vignettes, and visual ethnography, I expose how impairment effects are managed in ableist sporting environments that valorise normative athlete ideals. I interviewed 11 high-performance paraathletes, seven organisational representatives and two support workers. 
The research highlights the material, emotional, and temporal labour of care in highperformance sport. Findings are organised around three core themes: the embodied labour of care, impairment effects and interdependence; the tension between crip time, care time, and performance time; the intersecting structural, institutional, and ableist barriers that shape and constrain highly impaired athletes’ participation in disability sport.  
The first theme shows how high-performance sport privileges autonomous, efficient, and normative bodies, while marginalising those whose messy, gritty embodied impairment effects demand more time, support, and interdependence. The findings bring to the fore biosocial, psycho-emotional costs of navigating care and its impact on athlete welfare. The second theme uncovers how the rhythms of highly impaired bodies disrupt the linear, clockbound time of high-performance sport, revealing the incompatibility between care time and high performance cultures. It highlights the vital yet invisible labour of support workers, ii unacknowledged in contemporary sporting discourse. The third theme addresses the barriers that highly impaired athletes face when navigating ableist institutional and organisational structures. It exposes the complexity of the ableist disability sporting landscape and the gap between duty of care rhetoric and practice. 
Ultimately, this thesis calls for a radical reimagining of disability sport, one that centres interdependence, affirms bodily difference, and addresses the structural failures that marginalise highly impaired athletes.

text: The embodied and lived experiences of welfare and care for highly impaired, high performance para-sport athletes in Aotearoa New Zealand Aligning with calls in critical disability studies to bring the body and impairment into disability sport, this thesis examines the welfare and care experiences of highly impaired athletes in high-performance sport. While a focus on athlete welfare has gained some international prominence, and a duty of care is increasingly invoked as an organisational and coaching responsibility, these developments remain largely disconnected from disability.  
The research is centred around two main objectives. First, to amplify the lived and embodied experiences of highly impaired, high performance disabled athletes as they prepare for, train, and compete in sport, and those who support them. Second, to understand how sporting institutions and regulations (within the broader context of government funding and national health care provision) influence welfare and care practices for high performance disabled athletes. 
Crip methodologies and Indigenous Māori storytelling methodologies such as pūrākau centres lived experience as a site of resistance and knowledge production. Using a reflexive, qualitative approach, including semi-structured interviews, autoethnographic vignettes, and visual ethnography, I expose how impairment effects are managed in ableist sporting environments that valorise normative athlete ideals. I interviewed 11 high-performance paraathletes, seven organisational representatives and two support workers. 
The research highlights the material, emotional, and temporal labour of care in highperformance sport. Findings are organised around three core themes: the embodied labour of care, impairment effects and interdependence; the tension between crip time, care time, and performance time; the intersecting structural, institutional, and ableist barriers that shape and constrain highly impaired athletes’ participation in disability sport.  
The first theme shows how high-performance sport privileges autonomous, efficient, and normative bodies, while marginalising those whose messy, gritty embodied impairment effects demand more time, support, and interdependence. The findings bring to the fore biosocial, psycho-emotional costs of navigating care and its impact on athlete welfare. The second theme uncovers how the rhythms of highly impaired bodies disrupt the linear, clockbound time of high-performance sport, revealing the incompatibility between care time and high performance cultures. It highlights the vital yet invisible labour of support workers, ii unacknowledged in contemporary sporting discourse. The third theme addresses the barriers that highly impaired athletes face when navigating ableist institutional and organisational structures. It exposes the complexity of the ableist disability sporting landscape and the gap between duty of care rhetoric and practice. 
Ultimately, this thesis calls for a radical reimagining of disability sport, one that centres interdependence, affirms bodily difference, and addresses the structural failures that marginalise highly impaired athletes.

year: 2025-10