Document Type

Dissertation

Date of Degree

Summer 2016

Degree Name

PhD (Doctor of Philosophy)

Degree In

Human Toxicology

First Advisor

Gabriele Ludewig

Second Advisor

Laurence Fuortes

Abstract

Polychlorinated biphenyls (PCBs) are synthetic organic compounds that resist natural breakdown in the environment. Various toxic metals are found naturally in the earth and may become concentrated as a result a human activity. PCBs and toxic metals are a major public health concern due to human exposure from both natural and anthropogenic sources. Humans may be exposed to these chemicals from occupational sources, ingestion through food, drinking water and some medications. The main risk arising from environmental pollution by toxic metals and PCBS is damage to the nervous system. This thesis set out to answer two questions 1) does co-exposure to toxic metals and PCBs happen from occupational sources since these chemicals are present in various building materials? 2) Does co-exposure to Pb and the most abundant and neurotoxic PCBs (such as PCB153 or PCB95) generate more toxicity on neurons as compared to exposure to a single toxicant? To investigate whether co-exposure occurs from occupational sources, toxic metals and PCB (in progress) levels of 84 construction workers in eastern Iowa were assessed. Levels of DNA damage and antioxidant proteins associated with these exposures were also evaluated. The results revealed a wide range of Pb, Cd, and Hg levels in construction workers. Levels of DNA damage and levels of 8-Oxo-dG in these workers were influenced by whether they handled fluorescent light ballasts, whether they ate fish and whether they wore protective masks.

To answer the second question a PC12 cell line was used, a well-known model for dopaminergic (DA) neurons, to study the effect of single and co-exposure on cell viability, DA level, DA metabolism, DA synthesis and packaging enzyme expression and antioxidant enzyme expression. The results illustrate that effects of single exposure to Pb, PCB153 and PCB95 and the combination of Pb and PCB153 or PCB95 following 12 and 24h exposure are variable and the effects are based on different mechanisms. Likewise, PCB153 and PCB95 which are both non-dioxin like PCBs were found to have different effects on PC12 cells based on the structure of the congener. This thesis demonstrates for the first time that PCB153 or PCB95 synergistically increase Pb toxicity to neurons, however, more research is needed to explore the interactions and the mechanisms which are involved in the influence of Pb in the presence of PCB.

Pages

xiii, 153 pages

Bibliography

Includes bibliographical references (pages 123-142).

Copyright

Copyright 2016 Sabah Hassain Enayah

Included in

Toxicology Commons

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