Microarray analysis of biotransformation gene expression in human fetal liver and lung

Abstract

To identify biotransformation genes that are selectively expressed in human lung during fetal development, we performed a microarray analysis using RNA samples from the liver and lung of four fetuses at GD91-GD103. An analysis of biological themes for genes differentially expressed in the two tissues indicated that, at this stage, biological pathways for development and organogenesis were much more active in the lung than in the liver, whereas various metabolic pathways were much more active in the liver than in the lung. A comparison of biotransformation gene expression in the liver and lung indicated that CYP2R1, CYP2W1, CYP26B1, and CYP46A1 were detected only in the lung, and that ADH1B, ALDH1A2, CES1, FMO2, GSTM1, and GSTM5 were expressed at ≥2-fold higher levels in the lung than in the liver, findings that suggest metabolic capabilities of the fetal lung toward endogenous and exogenous compounds. In additional studies, a comparison of gene expression levels in liver, lung, and nasal mucosa among differing fetuses of similar gestational ages led to the identification of more than 40 genes that were expressed at much higher, or lower, than average levels in at least one fetus. Further studies to identify genetic polymorphisms that are associated with the interindividual differences in gene expression are under way. (Supported in part by NIH grants CA092596)