Lead Exposure and Gene Expression

The primary objective of this work was to analyze global gene expression patterns occurring in Fisher 344 rat livers exposed to varying levels of lead. Results showed differentially expressed genes including genes cited in the literature and several not previously reported to be affected by lead toxicity. Expression profiles were clustered and gene ontology (GO) revealed 15 GO categories affected by chronic (90d) exposure, while 3 GO categories were affected during (30d) exposures. Pathways emphasized the importance of Pb in modulating various cellular events in a manner similar to calcium regulation, including calcium signaling phosphorylation and dephosphorylation, histone acetylation and deacetylation. Conclusions include: Pb controls mammalian protein synthesis via regulating phosphorylation or dephosphorylation events of eukaryotic elongation/initiation factors; Pb regulates gene expression through the regulation of histone acetylases and Pb regulates calcium dependent transcription factor myocyte enhance factor-2. Quantitative PCR was employed in validating the microarray result and showed that Microarrays and qRT-PCR yield comparable results.