The Comparative Toxicogenomics Database's 10th year anniversary: update 2015.

Ten years ago, the Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) was developed out of a need to formalize, harmonize and centralize the information on numerous genes and proteins responding to environmental toxic agents across diverse species. CTD's initial approach was to facilitate comparisons of nucleotide and protein sequences of toxicologically significant genes by curating these sequences and electronically annotating them with chemical terms from their associated references. Since then, however, CTD has vastly expanded its scope to robustly represent a triad of chemical-gene, chemical-disease and gene-disease interactions that are manually curated from the scientific literature by professional biocurators using controlled vocabularies, ontologies and structured notation. Today, CTD includes 24 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, phenotypes, Gene Ontology annotations, pathways and interaction modules. In this 10th year anniversary update, we outline the evolution of CTD, including our increased data content, new 'Pathway View' visualization tool, enhanced curation practices, pilot chemical-phenotype results and impending exposure data set. The prototype database originally described in our first report has transformed into a sophisticated resource used actively today to help scientists develop and test hypotheses about the etiologies of environmentally influenced diseases.

[Genetic toxicology: findings and challenges].

The review highlights the history of genetic toxicology as a distinct research area, as well as the issues of genetic toxicology and development of its methodology. The strategies and testing patterns of genotoxic compounds are discussed with the purpose of identifying potential human carcinogens, as well as compounds capable of inducing heritable mutations in humans. The main achievements of genetic toxicology in the 20th century are summarized and the challenges of the 21st century are discussed.

Building on the past, shaping the future: the Environmental Mutagenesis and Genomics Society.

In late 2012, the members of the Environmental Mutagen Society voted to change its name to the Environmental Mutagenesis and Genomics Society. Here, we describe the thought process that led to adoption of the new name, which both respects the rich history of a Society founded in 1969 and reflects the many advances in our understanding of the nature and breadth of gene-environment interactions during the intervening 43 years.

Looking back to the future: from the development of the gene concept to toxicogenomics.

Initial progress in the science of 'genetics' in the first half of the 20th century was mainly driven by studies utilizing mutations and consequent changes in phenotype. The structural and functional nature of the gene was far from being understood. That state of understanding started changing from the 1940s. In the following decades, with the discovery of the double helix followed by the discoveries on gene structure and expression, there was a period when the structural and functional aspects of the gene could be conceived in terms of one entity, the cistron. However, the discovery of intervening sequences caused this unified concept to fall apart, making the gene concept a subject of philosophical debate again. Meanwhile, over time, technological progress in molecular biology had the field forge ahead rapidly, ultimately leading to the sequencing of the human genome and genomes of other species, and giving birth to the science of genomics. Developments in genomics have given rise to certain applied sub-disciplines like pharmacogenomics and toxicogenomics. While the full potential of pharmaco- and toxicogenomics is yet to be harnessed, they nevertheless have had an impact in drug development and safety assessment, such that the future promise of genomics seems achievable. At present, it is a good opportunity to revisit the path from the development of the initial gene concept and the philosophical debate surrounding the meaning of the term 'gene' to the current state of understanding of genes and genomes and their role in health and disease.

Fifty years of cytogenetics: a parallel view of the evolution of cytogenetics and genotoxicology.

A parallelism exists between human cytogenetics and cytogenetic toxicology. The breakthroughs, mostly coming from and used in clinical genetics, are widely used in genetic toxicology. The birth of human cytogenetics occurred in 1956 when it was published that the diploid number of chromosomes in humans is 46. The first stage in chromosome-induced mutagenesis began in 1938 when Sax published the effects of X-rays on the chromosomes of Drosophila. In 1959, the cytogenetic anomalies for Down, Klinefelter, and Turner syndromes were described, and parallelly in 1960, the first publication on chromosomal aberrations in man caused by ionizing radiation appeared. The cytogenetic analysis of chromosomal aberrations in cell cultures is considered one of the primary methods to evaluate induced mutagenesis. At the end of the 1960s, banding techniques allowed chromosomes to be individually identified, in parallel, the sister chromatid exchange analysis technology was described. Another milestone in the history of induced mutagenesis was the discovery that mutagenic agents were able to alter chromosomal division and segregation in gonads inducing meiotic nondisjunction. Here we review new approaches and applications such as biological dosimetry, translocation scoring using FISH, and micronucleus test. Chromosomal aberrations and micronucleus test are now effective cytogenetic biomarkers of early effect used as cancer predictors. Human cytogenetics has proven to be effective over its 50-year lifespan and, although each new technique that has appeared seemed to announce its end, the fact is that the current state of cytogenetics is in reality a collection of techniques that, while common, are cheap, fast, and wide-ranging. Therefore, in genotoxicology, they continue to be useful to identify mutagenic agents as well as to evaluate and analyze exposed populations.

The emergence of toxicogenomics: a case study of molecularization.

This paper described the efforts of scientists at the National Institute of Environmental Health Sciences (NIEHS) and their allies in the National Toxicology Program to molecularize toxicology by fostering the emergence of a new discipline: toxicogenomics. I demonstrate that the molecularization of toxicology at the NIEHS began in a process of 'co-construction'. However, the subsequent emergence of the discipline of toxicogenomics has required the deliberate development of communication across the myriad disciplines necessary to produce toxicogenomic knowledge; articulation of emergent forms, standards, and practices with extant ones; management of the tensions generated by grounding toxicogenomics in traditional toxicological standards and work practices even it transforms those standards and practices; and identification and stabilization of roles for toxicogenomic knowledge in markets and service sites, such as environmental health risk assessment and regulation. This paper describes the technological, institutional, and inter-sectoral strategies that scientists have pursued in order to meet these challenges. In so doing, this analysis offers a vista into both the means and meanings of molecularization.

Where is toxicology headed in the future?

Herbert Remmer was a pioneer in the study of the phenomenon of enzyme induction. He was also a leading figure, if not the foremost, in the development of the discipline of toxicology in Germany during his tenure as Professor of Toxicology at the University of Tübingen. Included here are some brief thoughts about where toxicology came from, where it is today, and what the future is. Toxicology is at a crossroads today, at an interface between basic science and applied projects. From its past as a descriptive discipline, it has incorporated a medley of concepts and technology from basic science. The usefulness of many approaches is now being evaluated. The hope is that toxicology will be able to be much more predictive in the future; a great need exists in the pharmaceutical industry. The shape of academic toxicology is also changing.