Year of Publication

2017

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department

Toxicology and Cancer Biology

First Advisor

Dr. Gang Chen

Second Advisor

Dr. Jia Luo

Abstract

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively.

Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro model system, the present study assessed the effects of Cr(VI) on T cell functions, as the first step of our investigation of the mechanism underlying Cr(VI)-inhibited immunosurveillance and carcinogenesis. Our results showed that Cr(VI) decreased the viability of CD4+ and CD8+ T cells, inhibited T cell activation, functions, including cytokine release, and degranulation.

Fetal ethanol (ETOH) exposure can damage the developing central nervous system and lead to cognitive and behavioral deficits, known as fetal alcohol spectrum disorders (FASD). The use of animal models, especially mouse models is essential for investigating the neurogenetic mechanism of fetal ETOH effects and screening pharmacotherapies against it, due to the extensive knowledge of mouse genetics. However, the availability of mouse model is limited. Via adopting various dosage, timing and administration routes of ETOH exposure, we developed two mouse models to assess behavioral or cognitive changes caused by fetal ETOH exposure in pre-weaning and adolescent period. Our results show that high dosage of ETOH exposure (4 g/kg) during PD 4-10 resulted in hyperactivity, disinhibition, and deficits in learning and memory in mouse offspring, which lays the groundwork for the future FASD research.

Digital Object Identifier (DOI)

https://doi.org/10.13023/ETD.2017.482

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