- Title
- The consequences of acrylamide exposure on the male germ line
- Creator
- Nixon, Belinda Jean
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2014
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Acrylamide is a commonly used industrial compound; however it is also naturally occurring in cooked foods such as potatoes, breads and coffee. Since the discovery of acrylamide formation in food, significant research has been carried out to determine the consequences of human dietary exposure to acrylamide. The reproductive toxicity of acrylamide was the focus of this thesis; however the compound is also known to cause neurotoxicity, carcinogenicity and genotoxicity. In rodent studies, acrylamide reproductive toxicity is primarily mediated through paternal exposure, and has been observed to induce DNA damage, male infertility, dominant lethality, heritable translocations and embryo resorptions. Thus, prolonged exposure to acrylamide in males not only has implications within the individual, but may have consequences for future offspring. The aims of this thesis were to examine the nature of DNA damage induced by acrylamide in male germ cells, and to investigate whether this damage could be induced at levels equivalent to human estimates. These aims were addressed using a series of experiments in isolated mouse germ cells, as well as a chronic exposure study in which acrylamide was administered to male mice via the drinking water for one year. Genome-wide microarray analyses were subsequently used to explore the molecular mechanisms that mediate the damage induced in the testis of acrylamide exposed mice. The results of this study indicated that acrylamide-mediated DNA damage was likely due to the presence of both DNA adducts as well as oxidative damage in mouse male germ cells. Furthermore, chronic exposure to acrylamide in male mice led to significant dose and time-dependent increases in DNA damage in male germ cells. Microarray analyses offered insight into the mechanisms that generate deleterious effects in the testes of mice following acrylamide exposure, and identified several potential biomarkers of exposure. The outcomes of this research will provide better understanding of acrylamide toxicity and shed light on the consequences of xenobiotic exposure in the male.
- Subject
- acrylamide; glycidamide; DNA damage; spermatogenesis; chronic; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1045465
- Identifier
- uon:14465
- Rights
- Copyright 2014 Belinda Jean Nixon
- Language
- eng
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