The overall pat tern of affected gene sets in cod larvae in the different exposure groups suggest that the way oil droplets are generated have an effect on toxicity in fish larvae. By comparing the alteration in gene transcription in cod larvae exposed to the highest concentrations of either chemically or mechanically dispersed oil directly, the chemically dispersed Inhibitors,Modulators,Libraries oil affected transcription of genes involved nucleosome regulation, i. e. genes encoding proteins participating in DNA replication and chromatin formation and regulation of cell proliferation, whereas the mechanically dispersed oil mainly affected genes encoding proteins involved in proteasome mediated protein degrad ation. Compared to larvae in the control group, the GSEA data showed that mechanically dispersed oil also mediated a general down regulation of many tran scripts in cod larvae in the MDH group.
Inhibitors,Modulators,Libraries IPA was used to evaluate whether or not chemically dis persed oil mediated a different toxic response compared to mechanically dispersed oil. Since IPA only can map mammalian homolog identifiers, GeneCards IDs were submitted for biological function and pathway analysis, using top BlastX hits and assuming orthologous genes have the same function. For example, because fish often have two isoforms of many genes due to genome dupli cation, labeled A and B, mammalian homolog identifiers had to be used as input for the IPA analysis, without knowing the exact function of the separate teleostean isoforms. The number of mapped IDs for IPA analysis in the different exposure groups were, CDH 583 out of 652, CDM 75 out of 85, CDL 13 out of 16, MDH 1501 out of 1680, MDM 101 out of 120 and MDL 30 out of 33.
According to Anacetrapib the IPA Core Analyses, using a maximum number of 70 molecules in each path way, the top affected networks in the cod larvae exposed Inhibitors,Modulators,Libraries to the highest concentration of chemically dispersed oil were RNA post transcriptional modifica tion, cellular assembly and organization, cell morphology with a score of 98, DNA replication, recombination, and repair, cell cycle, cancer with a score of 84 and Lipid me tabolism, molecular transport, small molecule biochemis try with a score of 65.
The corresponding top affected pathways in the cod Inhibitors,Modulators,Libraries larvae exposed to mechanically dis persed oil were RNA post transcriptional modification, cellular assembly and organization, cell morphology with a score of 75, Cellular function and maintenance, small molecule biochemistry, DNA replication, recombination, and repair with a score of 66, and Lipid metabolism, small molecule biochemistry, vitamin and mineral metab olism with a score of 62. IPA Tox is a data analysis capability within IPA that delivers a focused toxicity assessment of input molecules using toxicogenomics approaches. Table 2 shows the sig nificant IPA Tox pathways in the six groups of cod lar vae exposed to oil dispersants.