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In this thesis, the genotoxic potential of andrographolide, which is a primary phytochemical of an annual herb Andrographis paniculata, was assessed and the possible mechanisms of action were elucidated. In silico predictions showed that andrographolide may be capable of inducing skin sensitisation and chromosome damage in mammals in vitro and the identification of possible metabolites. Andrographolide was demonstrated to induce micronuclei formation in vitro in three cell lines tested namely AHH-1, MCL-5 and V-79. In AHH-1 and V-79 cell lines, the highest frequency of micronuclei was recorded at 30 muM whereas in MCL-5 cell line, 50 p,M of the compound was necessary to elicit similar damage, which may be due differences in cellular metabolism capacity. The phytochemical was shown to cause dose-dependent cellular cytotoxicity in all the cell lines tested with cells dying primarily via necrosis compared to apoptosis and effectively reduced cell number. Kinetochore labelling on MCL-5 cells challenged with increasing doses of andrographolide revealed that the phytochemical acts in aneugenic manner evident from the increment in kinetochore-positive micronuclei. The compound of interest was also found to disrupt segregation fidelity via centrosome amplification resulting in chromosomal aberration. The presence of extra microtubule organising centres may play a role in the promotion of aberrant mitoses. Disruption to normal cell division was observed even after the removal of the compound in vitro. Mammalian HFRT point mutation assay using AHH-1 cell line revealed that andrographolide induced mutation evident from HPRT- mutant colonies formation between 5muM and 30muM. The phytochemical was also found to exert cytotoxicity in a concentration-dependent manner between 1muM and 50muM. Thus, andrographolide is capable of disrupting normal mammalian cell division and causing dose-dependent cytotoxicity in vitro.

The awareness on the importance of managing knowledge as the most important assets that need to be fully utilised has become the key competitive issue lately. In Malaysia, the concern was not only from companies but also from the Government of Malaysia itself. At the end of the year 2002, the Government of Malaysia has launched the Knowledge-based Economy Master Plan which aims to propel Malaysia from a production-based economy to a knowledge-based economy. With an increasing concern to create a knowledgeable society, it is critically important to understand the nature of such knowledge that is already embedded in the organisation's business processes, and how that knowledge is used as an important source of competitive advantage. The overall aim of this thesis is to analyse the current situation on how knowledge is managed in the public organisation in Malaysia and to provide government agencies in Malaysia with data on how knowledge is transferred. The primary focus of the study is to identify the organisational elements that are important for the transfer of knowledge in the public organisations in Malaysia. The study also examines different lengths of working experiences and number of years in an organisation has an impact on the understanding of knowledge management in the public organisation. After a literature review, and the development of conceptual frameworks, a number of hypotheses are put forward. To achieve an in-depth study, the Ministry of Entrepreneur Development of Malaysia was chosen as a case study. A questionnaire was used as the main instrument in gathering data and interview(s) for the key informants were also conducted. A total of 154 respondents were involved in the survey and five key informants were interviewed. The questionnaire is principally concerned with the understanding of knowledge management in the Ministry and the questions on the variables that are used for the hypothesis testing. The study also investigates the relationship between organisational elements and the performance of knowledge transfer. Five main independent variables were identified - organisational culture, organisational structure, technology, people/human resources and political directives - and these were tested against knowledge transfer performance. The results reveal that there are two independent variables that have significant relationships to the performance of knowledge transfer. The variables are sharing culture and ICT know-how. Therefore, it is necessary for organisations to consider some of the elements that shows a relationship between the tested variables in implementing a knowledge management strategy in an organisation. However, certain variables that did not show any relationship should not be ignored totally, as they are still very important for some organisations. The study shows that knowledge management as a practice would be the most influential strategy in managing knowledge in public organisations in Malaysia in the near future. On the basis of the research findings the researcher is able to put forward a series of recommendations, particularly in formulating a knowledge management strategy that is suitable for the public organisation in Malaysia which complements the Knowledge-based Economic Master Plan that was launched by the Government.