Is gene expression altered by exposure to DBP in a cell culture model?
Phthalates are widely used in industrial processes and household products and as a result are amongst the most commonly encountered environmental pollutants worldwide. Humans are exposed to them directly via their use in cosmetics, medicines, as plasticisers in various products, medical devices and in children’s toys, and indirectly via the environment where they are ubiquitous contaminants due to their industrial, domestic, and agricultural uses. Dibutylphthalate (DBP) was widely used as an insecticide by New Zealand troops stationed in Malaya during the 1950s, and there are reports of increased rates of reproductive abnormalities in children of these veterans. This thesis set out to explore the possible effects of DBP exposure on genes that control testosterone metabolism. To do this, an appropriate cell line was selected, and DBP exposure experiments were conducted. Quantitative reverse transcriptase polymerase chain reaction assays for several key steroidal pathway genes were established, and used to explore possible effects of DBP exposure on expression of these genes. The HSD17, CYP17, CYP11 HSD3 and StAR genes were examined, and only changes in StAR gene expression due to DBP in high (10μg/mL), medium (1 μg/mL) and low (0.1 μg/mL) doses were studied. The results indicated that StAR mRNA was upregulated following exposure to a high dose of DBP in the THP1 cell line. On the other hand, exposure to medium and low doses of DBP showed no effect on StAR mRNA expression. Despite the limited results obtained in this study, analysis of gene expression changes in the THP1 cell line after exposure to DBP represents a potential model system that may be useful for future work in this area.
Advisor: Keenedy, Martin
Degree Name: Master of Science
Degree Discipline: Biochemistry
Publisher: University of Otago
Research Type: Thesis