Abstract
Genotoxicity testing is an important component of toxicity assessment. As illustrated by the European registration, evaluation, authorization, and restriction of chemicals (REACH) directive, it concerns all the chemicals used in industry. The commonly used in vivo mammalian tests appear to be ill adapted to tackle the large compound sets involved, due to throughput, cost, and ethical issues. The somatic mutation and recombination test (SMART) represents a more scalable alternative, since it uses Drosophila, which develops faster and requires less infrastructure. Despite these advantages, the manual scoring of the hairs on Drosophila wings required for the SMART limits its usage. To overcome this limitation, we have developed an automated SMART readout. It consists of automated imaging, followed by an image analysis pipeline that measures individual wing genotoxicity scores. Finally, we have developed a wing score-based dose-dependency approach that can provide genotoxicity profiles. We have validated our method using 6 compounds, obtaining profiles almost identical to those obtained from manual measures, even for low-genotoxicity compounds such as urethane. The automated SMART, with its faster and more reliable readout, fulfills the need for a high-throughput in vivo test. The flexible imaging strategy we describe and the analysis tools we provide should facilitate the optimization and dissemination of our methods.
Highlights
Genotoxicity can occur from a chemical compound causing damage to the genetic material, resulting in disease and/or death
Genotoxicity is an important consideration in toxicity regulations
Introducing a faster, more scalable, in vivo test would benefit public and worker safety in all sectors of industry, as it would allow more systematic and reliable testing of the chemicals with which we come into contact daily
Summary
Genotoxicity can occur from a chemical compound causing damage to the genetic material, resulting in disease and/or death. Automated SMART for Genotoxicity more common across various industries [1,2,3] including pharmaceutical, cosmetic, and automobile manufacturing industries, among others These regulations were created to ensure the safety of the public as well as workers exposed to various chemical agents involved in the manufacturing process of different products. Compounds undergo a number of complementary in vitro and in vivo tests to enable the prediction of such effects [6] The latter class of tests involves small animals such as rodents. In addition to the ethical problems associated with research in mammals, these tests can be quite costly and time consuming [7] For this reason, in vivo tests are usually carried out after or just before the selection of the lead compound
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