Effect of waterborne exposure to carcinogenic PAHs on adult zebrafish hepatic transcriptome

ABSTRACT: Several environmental pollutants, especially organic compounds such as polycyclic aromatic hydrocarbons (PAHs) are potent carcinogenic chemicals. Exposure of different fish species to PAHs causes a high prevalence and variety of tumor lesions. To identify and compare the mode of action (MOA) of different model carcinogenic PAHs, a transcriptomic study was carried out in adult zebrafish (Danio rerio) after exposure to 0.3 mg/l of benzo(a)pyrene (B(a)P) or to 7,12-dimethylbenz(a)anthracene (DMBA), both of them dissolved in dimethyl sulfoxide (DMSO; final concentration of 0.01%). Samples for microarray analysis were taken after 1 and 2 weeks of exposure. The changes in the mRNA transcription levels over the corresponding controls were compared among treatments. Correspondence analysis was able to discriminate among treatments; factor 1 separated both sampling times while factor 2 separated the compounds. A total number of 3043 transcripts was shown to be differentially regulated in at least one of the treatments. B(a)P treatment produced regulation of sequences related to GO categories associated to cell cycle and cell division whereas DMBA regulated GO terms related to oxidation/reduction responses, responses to chemicals and response to bacterium. Both compounds were able to alter many xenobiotic metabolism related genes, especially upregulating the transcription of phase I metabolism-related genes such as cytochrome P450 members (cyp1a or cyp1b), and many cancer-related genes such as the Jun B proto-oncogene (junb). Overall, these results indicated that the exposure to both PAHs was able to differentially alter the transcription levels of genes involved in both the detoxification metabolism and the cell-cycle control, including different tumor-supressor genes and oncogens. These alterations have been often related to the appearance of tumor lesions.

ORGANISM(S): Danio rerio

PROVIDER: GSE43675 | GEO | 2013/10/01

SECONDARY ACCESSION(S): PRJNA187042

REPOSITORIES: GEO