Toxicogenomic analysis of hepatic gene expression following exposure to persistent organic pollutants
Ovando, Bladimir J.
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Persistent organic pollutants (POPs) represent an array of environmental contaminants with have been linked to numerous adverse biological effects, have long half-lives and have the capacity for long range transport. The four POPs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 2,2',4,4',5,5',-hexachlorobiphenyl (PCB153), were examined by the National Toxicology Program (NTP) during a series of two-year cancer bioassays to evaluate the toxic and carcinogenic effects of these compounds. Significant increases in the incidence of neoplastic and non-neoplastic lesions were observed in the livers of female Sprague-Dawley rats chronically exposed to TCDD, PCB126 and a binary mixture of PCB126 and PCB153. PeCDF caused significant increases in numerous non-neoplastic lesions but no neoplastic lesions and single exposure to PCB153 primarily induced the formation of liver hypertrophy. The toxic effects of compounds such as TCDD and PCB126 are believed to be the primary result of binding and activation of the cytosolic transcription factor, the aryl hydrocarbon receptor. The studies presented in this dissertation discuss the toxicogenomic analysis of hepatic gene expression conducted in an effort to identify gene expression changes that may be contributing to the liver pathology observed by the NTP with chronic exposure to TCDD and related compounds.