Project description:To identify molecular effects of the antineoplastic agent PKC412 (Midostaurin), we applied gene expression profiling in zebrafish using whole genome microarrays. Zebrafish eleuthero-embryos were exposed for 6 dpf to nominal levels of 2 μg/L and 40 μg/L PKC412. Among the 259 and 511 altered transcripts at both concentrations, respectively, the expressions of genes involved in the circadian rhythm were of interest. Alteration of swimming behaviour was not noted. Pathways of interest affected by PKC412 were angiogenesis, apoptosis, DNA damage response and response to oxidative stress. Angiogenesis was not altered by PKC412 treatment at both concentrations. Apoptosis occurred in olfactory placodes of embryos exposed to 40 μg/L, and DNA damage was induced at both PKC412 concentrations. However, there were no significant effects on reactive oxygen species formation. This study leads to the conclusion that PKC412-induced alterations of gene transcripts are partly paralleled by physiological effects at high, but not at low PKC412 concentrations expected to be of environmental relevance.
