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: Key points of value in B2B intermediated electronic networks

authors: Gibb, Jenny L.

abstract: The Internet is an electronic network with open standards that is associated with the exchange of information at heightened levels of reach, richness, transparency, and speed often directly between buyers and suppliers. The growing prominence of the Internet has led to the blurring of industry boundaries, as well as the emergence of new online intermediaries, and the disappearance of traditional ones. Happening simultaneously has been the development of new modes of business such as the B2B (IE) network. When combining the characteristics of these business models with the increased efficiencies and reduced information processing costs associated with the Internet, it becomes important to identify these new value creating opportunities. Though the advantages of the Internet and associated models have been widely espoused, to date there has been scant empirical investigation into these areas. Furthermore, as networked trade grows in popularity, whether entering into online or offline trade opportunities, an ongoing understanding is required of this mode of business. Hence, this thesis has examined the question "Where are the key sources of value in a B2B (IE) network?" 
Structuration theory, situated within the mid-range theorising perspective has been used in this thesis as an ontological lens due to its recognition of the duality of structure between man and machine, with the business intermediary and Internet respectively. This lens has served to facilitate an examination of these two brokering bodies in the development of processes, rules, regulations, and relationships that are embedded within this network structure. My analysis and theoretical development attempt to build a bridge between the existing strategy, networks, and B2B (IE) networks literatures through the use of the grounded theory development approach by moving between a skeletal empirical framework and the data from three case studies. The first case study, M-co is a network that operates in the highly volatile New Zealand electricity industry to provide a bid/offer price mechanism. The second case study is Ecomex, a network that is positioned within the more moderately volatile New Zealand timber industry. It offers a range of price mechanisms, of which the negotiated method appears to be the one most favoured by traders. The third case study is EDIS, a network embedded within a more stable environment, offering a service to general product traders using a fixed price method. 
The key theoretical contribution that this thesis makes is the development of a dynamic model that identifies the network as the primary unit of analysis, with three secondary units of analysis: the informational unit, the relational unit, and the central core unit, each with separate underlying dimensions. Though these secondary units are important as individual entities in their own right, what is more important is the understanding of how these units interact in order to realise the full value creation potential in a B2B (IE) network. This interaction process was found to be led by the business intermediary, positioned in the central core.

text: Key points of value in B2B intermediated electronic networks The Internet is an electronic network with open standards that is associated with the exchange of information at heightened levels of reach, richness, transparency, and speed often directly between buyers and suppliers. The growing prominence of the Internet has led to the blurring of industry boundaries, as well as the emergence of new online intermediaries, and the disappearance of traditional ones. Happening simultaneously has been the development of new modes of business such as the B2B (IE) network. When combining the characteristics of these business models with the increased efficiencies and reduced information processing costs associated with the Internet, it becomes important to identify these new value creating opportunities. Though the advantages of the Internet and associated models have been widely espoused, to date there has been scant empirical investigation into these areas. Furthermore, as networked trade grows in popularity, whether entering into online or offline trade opportunities, an ongoing understanding is required of this mode of business. Hence, this thesis has examined the question "Where are the key sources of value in a B2B (IE) network?" 
Structuration theory, situated within the mid-range theorising perspective has been used in this thesis as an ontological lens due to its recognition of the duality of structure between man and machine, with the business intermediary and Internet respectively. This lens has served to facilitate an examination of these two brokering bodies in the development of processes, rules, regulations, and relationships that are embedded within this network structure. My analysis and theoretical development attempt to build a bridge between the existing strategy, networks, and B2B (IE) networks literatures through the use of the grounded theory development approach by moving between a skeletal empirical framework and the data from three case studies. The first case study, M-co is a network that operates in the highly volatile New Zealand electricity industry to provide a bid/offer price mechanism. The second case study is Ecomex, a network that is positioned within the more moderately volatile New Zealand timber industry. It offers a range of price mechanisms, of which the negotiated method appears to be the one most favoured by traders. The third case study is EDIS, a network embedded within a more stable environment, offering a service to general product traders using a fixed price method. 
The key theoretical contribution that this thesis makes is the development of a dynamic model that identifies the network as the primary unit of analysis, with three secondary units of analysis: the informational unit, the relational unit, and the central core unit, each with separate underlying dimensions. Though these secondary units are important as individual entities in their own right, what is more important is the understanding of how these units interact in order to realise the full value creation potential in a B2B (IE) network. This interaction process was found to be led by the business intermediary, positioned in the central core.

year: 2004

title: The "false generosity" of treaty settlements: innovation and contortion

authors: Te Aho, Linda

abstract: In Aotearoa New Zealand the ways in which indigenous claims to lands and waters are addressed are often looked to as good, or even best, practice by indigenous peoples around the world. While things are far from perfect, in recent decades Maori have succeeded in changing perceptions about the Treaty of Waitangi as the foundation of the nation, and work steadily continues on settling outstanding Treaty claims. The resulting Treaty of Waitangi settlements are negotiated arrangements which aim to remove a sense of historical grievance and achieve significant rebuilding of the Maori economy. They are seen by some as dynamic and powerful steps towards economic independence, as a means of recognising special relationships to lands and waters, and a necessary prerequisite to improved relationships between the state and the indigenous Maori in the future. ¹ Critics see the settlements and the processes followed to reach them as too heavily weighted in the government's favour. ² They argue that the settlements do not sufficiently compensate for actual losses. They are said to pit Maori against Maori. Diverse claimant groups are effectively forced to negotiate within standardised and fixed parameters. For these and other reasons, the settlement agreements, policies and processes have been labelled as divisive and compromising self-determination. ³

text: The "false generosity" of treaty settlements: innovation and contortion In Aotearoa New Zealand the ways in which indigenous claims to lands and waters are addressed are often looked to as good, or even best, practice by indigenous peoples around the world. While things are far from perfect, in recent decades Maori have succeeded in changing perceptions about the Treaty of Waitangi as the foundation of the nation, and work steadily continues on settling outstanding Treaty claims. The resulting Treaty of Waitangi settlements are negotiated arrangements which aim to remove a sense of historical grievance and achieve significant rebuilding of the Maori economy. They are seen by some as dynamic and powerful steps towards economic independence, as a means of recognising special relationships to lands and waters, and a necessary prerequisite to improved relationships between the state and the indigenous Maori in the future. ¹ Critics see the settlements and the processes followed to reach them as too heavily weighted in the government's favour. ² They argue that the settlements do not sufficiently compensate for actual losses. They are said to pit Maori against Maori. Diverse claimant groups are effectively forced to negotiate within standardised and fixed parameters. For these and other reasons, the settlement agreements, policies and processes have been labelled as divisive and compromising self-determination. ³

year: 2017