REVIEW Toxicogenomics using yeast DNA microarrays Daisuke Yasokawa 1, ⁎ and Hitoshi Iwahashi 2 Hokkaido Food Processing Research Center, Department of Food Development, 589-4 Bunkyodai Midorimachi, Ebetsu, Hokkaido 0690836, Japan 1 and Health Technology Research Center (HTRC), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba-Nishi 3A, 16-1, Onogawa, Tsukuba, Ibaraki 3058569, Japan 2 Received 8 March 2010; accepted 4 June 2010 Available online 10 July 2010 Development of genomics and bioinformatics enable us to analyze the global gene expression profiles of cells by DNA microarray. Changes in gene expression patterns indicate changes in its physiological conditions. Following the exposure of an organism or cell to toxic chemicals or other environmental stresses, the global genetic responses can be expeditiously and easily analyzed. Baker's yeast, Saccharomyces cerevisiae, is one of the most studied and useful model eukaryotes. The biggest advantage of yeast genomics is the available functional information for each gene and a considerable number of data are accumulating in the field of toxicity assessment using yeast DNA microarray. In this review, we discuss the toxicogenomics of metal ions, alcohols and aldehydes, and other chemicals. © 2010, The Society for Biotechnology, Japan. All rights reserved. [Key words: DNA microarray; Saccharomyces cerevisiae; Toxicogenomics; Transcriptome] According to the Chemical Abstract service (http://www.info.cas.org), there are more than 47 million chemicals that have been found and identified, and more than 70,000 of them are utilized in agriculture and industry. However, the spread of toxic chemicals in the environment is not well understood. Conventional environmental risk assessment is mainly based on chemical analysis to identify the source of the toxicity. With this approach, only about 10% of the chemicals can be analyzed even with the latest technology and there are still detection limits for some of these chemicals (1). Furthermore, the degree of toxicity to organisms may not correlate with the concentrations of chemicals, especially in complex mixtures like environmental samples. In this context, environmental risk assessment using a bioassay is necessary. The bioassay is a versatile technology, which evaluates chemical toxicity using various organisms without identifying the individual toxic substances. Further, it is applicable to unknown or novel substances and complex mixtures. However, biomarkers are limited to growth inhibi- tion, survival, development, reproduction, and other specific biological responses and often satisfactory insight into the mode of toxicity cannot be obtained. In the classical bioassay of unknown materials, it can be difficult to differentiate between the toxicant and accompanying biological side effects. DNA microarray analysis is a powerful tool, which is expected to compensate for some of the flaws in the classical bioassay through simultaneous expression analysis of thousands of genes. Changes in gene expression patterns indicate changes in its physiological conditions. Following the exposure of an organism or cell to chemicals or other environmental stresses, the global genetic responses can be expeditiously and easily analyzed. It is the equivalent of simulta- neously performing thousands of northern blot hybridization experi- ments of all genes from the treated organism using thousands of specific probes. Organisms may upregulate a set of genes to excrete, modify, and degrade a toxicant, or to repair lesions. Genes may be downregulated to avoid incorporation of the toxicant or to prevent the lesion from worsening. The mRNA expression profiles can then be analyzed and interpreted to define the toxicity profile. Afshari et al. (2) and Nuwaysir et al. (3) have focused on the use of microarrays for toxicology analysis. They hypothesized that a microarray could be used in a bioassay for the prediction of chemical toxicity and environmental risk assessment. In this century, great progress has been made in the field of toxicogenomics and significant DNA microarray data has been accumulated. One of the most studied is the yeast DNA microarray, which can be used as a model to discuss specific examples of toxicant identification and the future application of microarray technology. In this review, we discuss the application of yeast cells as a model eukaryotic organisms and the use of DNA microarray technology for environmental and cellular toxicogenomics. We selected copper as a representative of the heavy metals, several organic compounds (methanol and formaldehyde), and other chemicals to review toxicogenomics using yeast DNA microarrays. The future application of toxicogenomics is also discussed. Journal of Bioscience and Bioengineering VOL. 110 No. 5, 511 – 522, 2010 www.elsevier.com/locate/jbiosc ⁎ Corresponding author. Tel.: +81 11 387 4118; fax: +81 11 387 4664. E-mail address: yasokawa-daisuke@hro.or.jp (D. Yasokawa). 1389-1723/$ - see front matter © 2010, The Society for Biotechnology, Japan. All rights reserved. doi:10.1016/j.jbiosc.2010.06.003