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Access Type

WSU Access

Date of Award

January 2015

Degree Type

Thesis

Degree Name

M.S.

Department

Nutrition and Food Science

First Advisor

Ahmad R. Heydari

Abstract

The objective of this study was to evaluate the Synergetic Effect of Permethrin and 1,2-Dimethylhydrazine (DMH) on Anti-oxidation and Damage Response genes. The animal models used for this study were 8 week old C57/blk6 female mice. The mice were fed a Folate Adequate (FA) diet. At 8 weeks, the mice were intraperitoneally injected with pesticides. Three 8-week old female mice were injected intraperitoneally with a mix of cis and trans permethrin (75%:25% respectively) at 30% median lethal dose (96 mg/kg body weight). Permethrin was dissolved in corn oil and injected 24 hours before sacrifice. In three other mice, DMH was also injected intraperitoneally 24 hours before sacrifice at 30 mg/kg body weight per mouse. Three mice were also injected 24 hours before sacrifice with a combination of DMH and permethrin at the same dosage. High levels of ACF formation and inflammation in the colon were seen in the mice injected with the combination of pesticides (combo) when compared to permethrin and DMH alone.

To determine synergism of the pesticides, levels of gene expression was measured using cDNA. Anti-oxidation gene expression studied was glutathione peroxidase (GPx), thioredoxin (TRX), thioredoxin reductase (TRXR), and Peroxiredoxin (PRDX). The damage response genes studied were Tumor Protein p53 (p53), Growth Arrest and DNA Damage (GADD45), Mamalian Target of Rapamycin (mTor), and Proliferating cell nuclear antigen (PCNA).

As a general trend, anti-oxidation genes had increased expression in mice given the combination of pesticides. An exception was the anti-oxidation gene TRXR which saw no change in expression. Damage response genes had unchanged levels of expression. An exception to this was p53 gene which saw increased expression in mice exposed to combo conditions.

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