Project description:Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon associated with developmental and neurobehavioral toxicity. This study examined whether parental BaP exposure produces transcriptional changes in the brains of unexposed adult first filial generation (F1) Japanese medaka. Adult parental fish were exposed to solvent control or 1 µg/L BaP for 21 days; eggs were collected after exposure and F1 offspring were reared in clean water. Whole brains from three control-lineage and three BaP-lineage adult males were analyzed by single-nucleus RNA sequencing. Fourteen transcriptionally distinct brain cell populations were resolved, and treatment-associated differential expression was evaluated within each cluster.
Project description:Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are produced by the incomplete combustion of organic matter and thus are present in tobacco smoke, charbroiled food and diesel exhaust. The nematode Caenorhabditis elegans lacks the genetic components of the classical mammalian cytochrome P450 (CYP)-mediated BaP-diol-epoxide metabolism pathway thus CYP1A1 or CYP1A2 together with human epoxide hydrolase (EPHX) was introduced into the worm genome, thereby allowing to study potential physiological, genomic and transcriptional changes after BaP exposure in these CYP-humanised C. elegans strains. Whole genome sequencing revealed a higher frequency of T>G base substitution mutations in worms expressing human CYP1A1;EPHX thereby demonstrating the amenity of introducing human genes into the C. elegans genome and their utility to serve as a model for environmental carcinogenesis and pharmacological research.
Project description:Inhibitors directed towards PARP1 and PARP2 are approved agents for the treatment of BRCA-related cancers. Other members of the PARP family have also been implicated in cancer and are being assessed as therapeutic targets in cancer and other diseases. In fact, an inhibitor of PARP7 (RBN-2397) has now reached early-stage human clinical trials. Here, we performed a genome-wide CRISPR screen for genes that modify the response of cells to RBN-2397. We identify the polycyclic aromatic hydrocarbon receptor AHR and multiple components of the cohesin complex as determinants of resistance to this agent. Activators and inhibitors of AHR modulate the cellular response to PARP7 inhibition, suggesting potential combination therapy approaches.
2022-04-06 | PXD028733 | Pride
Project description:Enrichment of Polycyclic Aromatic Hydrocarbon-Degrading Bacteria in Mangrove Wetland of Maowei Sea, Guangxi, China