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(American Journal of Pathology. 2003;163:2191-2199.)
© 2003 American Society for Investigative Pathology

Technical Advance

Liver Gene Expression Profiles of Rats Treated with Clofibric Acid

Comparison of Whole Liver and Laser Capture Microdissected Liver

Cécile Michel*{dagger}, Chantal Desdouets{dagger}, Béatrice Sacre-Salem*, Jean-Charles Gautier*, Ruth Roberts* and Eric Boitier*

From the Department of Drug Safety Evaluation,* Aventis Pharma, Vitry-sur-Seine, France; and INSERM U370,{dagger} Paris, France

Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor {alpha}, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci.




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