Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity.

摘要: A rate-limiting step that occurs in the drug discovery process is toxicological evaluation of new compounds. New techniques use small amounts experimental compound and provide a high degree predictivity would greatly improve this process. The field microarray technology, which allows one to monitor thousands gene expression changes simultaneously, rapidly advancing already being applied numerous areas toxicology. However, it remains be determined if compounds with similar toxic mechanisms produce transcriptional expression. In addition, must caused by an agent vitro reflect those produced vivo. order address these questions, we treated rat hepatocytes 15 known hepatoxins (carbon tetrachloride, allyl alcohol, aroclor 1254, methotrexate, diquat, carbamazepine, methapyrilene, arsenic, diethylnitrosamine, monocrotaline, dimethyl-formamide, amiodarone, indomethacin, etoposide, 3-methylcholanthrene) used technology characterize based on changes. Our results showed expressional profiles for indeed formed clusters, suggesting effect transcription. There was not complete identity, however, indicating each unique signature. These show large-scale analysis using has promise as diagnostic tool