Utilization of a toxicogenomic biomarker for evaluation of chemical-induced glutathione deficiency in rat livers across the GeneChip data of different generations.

Previously, we reported 69 probe sets (GSH probe sets) of RG U34A GeneChip that were useful for the evaluation of chemical-induced glutathione depletion in rat livers. The aim of the present study was to investigate whether these probe sets could be applied to the analysis of RAE 230A GeneChip data. Since a straightforward data comparison of RG U34A and RAE 230A GeneChips could not overcome the generation-dependent discrepancy in signal profiles, we tried two methods to improve the data compatibility between the two GeneChips.

Evaluation of glutathione deficiency in rat livers by microarray analysis.

Hepatic glutathione content was measured and gene expression data were obtained using an Affymetrix RG U34 array after treatment with tap water containing 20mM l-buthionine (S, R)-sulfoximine (BSO) to male F344 rats for four consecutive days. Both Spearman's and Pearson's correlation coefficients were calculated between the glutathione content and the mRNA content level obtained from the microarray analysis individually. Sixty-nine gene probes, which were statistically significant (Spearman's correlation, P < 0.

Molecular mechanism investigation of phenobarbital-induced serum cholesterol elevation in rat livers by microarray analysis.

Phenobarbital (PB) increases serum total cholesterol levels in rodents and humans. To investigate the underlying molecular mechanisms, we performed a microarray analysis on liver of rats treated repeatedly with 100 mg/kg PB, and examined the serum blood chemistry. The serum concentration of non-esterified fatty acids was decreased from day 1 to day 14 except for day 7, and that of cholesterol was increased from day 4 to day 14.

Effect of serum cholesterol on the mRNA content of amyloid precursor protein in rat livers.

Genes that showed mRNA content profiles, which correlated with serum concentrations of total cholesterol (T.CHO), were screened from the microarray data of phenobarbital (PB)- or clofibrate (CLO)-treated rat livers, and the correlation was evaluated based on Spearman's correlation coefficient. Many genes involved in the cholesterol or bile acid metabolism were highly correlated such as UDP-glucuronosyltransferase-21, apolipoprotein A-I and cMOAT.

Rat mutations cvd and hob with cerebellar malformations map to chromosome 2.

In this paper, we executed genome mapping and comparative mapping analyses for cvd and hob, autosomal recessive mutations with cerebellar vermis defect and cerebellar dysplasia in the rat. For the linkage analysis, we produced three sets of backcross progeny, (ACI x CVD)F(1) and (F344 x CVD)F(1) females crossed to a cvd homozygous male rat, and (HOB x WKY)F(1) males crossed to hob homozygous female rats. Analysis of the segregation patterns of simple sequence length polymorphism (SSLP) markers scanning the whole rat genome allowed the mapping of these autosomal recessive mutations to rat Chromosome (Chr) 2.

Phylogenetic tree facilitates the understanding of gene expression data on drug metabolizing enzymes obtained by microarray analysis.

The gene expression data of drug metabolizing enzymes (DMEs) in male F344 rat livers were examined after treatments with phenobarbital (PB), clofibrate (CPIB), 3-methylcholanthrene (3-MC) or butylated hydroxyanisole (BHA) using an Affymetrix GeneChip system. Nucleotide sequence-based phylogenetic trees combined with a heat map, that presents both quantitative and qualitative data, were created. Most DME gene probes were successfully classified into the corresponding gene families, although a few were not due to the presence of non-coding or promoter region sequences in the target gene.