Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effects of methoxychlor (MXC) in male largemouth bass

ABSTRACT: Male largemouth bass were injected with 25 mg/kg MXC and sacrificed after 48 hours; liver dissected and used for total RNA extraction Keywords: Methoxychlor injection; single injection and time point The organochlorine pesticide methoxychlor (MXC) (1,1,1-trichloro-2,2-bis(p-methoxyphenyl)ethane) has been used increasingly as an insecticide since the banning of DDT, the primary advantage being that MXC is rapidly metabolized and does not show high levels of bioaccumulation in non-target organisms. However, studies have shown that MXC can be metabolized into additional metabolites, such as mono-demethylated 2-(p-hydroxyphenyl)-2-(p-methoxyphenyl)-1,1,1-trichloroethane (OH-MXC) and bis-demethylated 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), both of which are estrogenic in mammals. In addition, there is increased potential for disruptions to normal hepatic physiology (Schlenk et al., 1998; Stuchal et al., 2006). The objectives of the present study were to study the hepatic genomic response in male largemouth bass to an i.p. injection of MXC. We performed a microarray analysis on 25 mg/kg MXC 48 hour injection because there was a significant induction of ERÎ± and ERÎ²b mRNA in the liver which was comparable to a 48 hour 1 mg/kg injection of E2 (previous work done by Blum et al., 2008; Aquat Toxicol. 86(4), 459-469). We chose the liver because of the significant role this tissue plays in detoxification of contaminants and due to the high capacity to produce vitellogenin in response to estrogenic chemicals. We were also interested in comparing the genomic response of MXC to estradiol alone to identify putative candidate genes and pathways that may be specific to MXC and not due to direct estrogenic effects mediated via E2 receptors. Largemouth bass injected with single i.p. with 25 mg/kg methoxychlor; sacrificed 48 days later,liver tissue studied. 4 individual liver samples (control and treatment)

ORGANISM(S): Micropterus salmoides

SUBMITTER: Dan Spade

PROVIDER: E-GEOD-12700 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Cadmium is a natural element that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 Âµg/kg of cadmium chloride and microarray analyses were conducted in the liver and testis 48 hours after injection. Transcriptomics profiles identified in response to cadmium treatment were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testes. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a proposed marker of cadmium exposure, showed a small insignificant increase after 48 hours exposure. Carbohydrate metabolic pathways were also disrupted in cadmium-exposed fish with hepatic transcripts such as UDP-glucose pyrophosphorylase 2 and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signalling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly increased in the liver including genes encoding for the rate limiting steroidogenic acute regulatory protein and the catalytic enzyme 7-dehydrocholesterol reductase. Integration of the transcriptomics data using functional enrichment analyses revealed a number of enriched gene networks associated with previously reported adverse outcomes of cadmium exposure such as liver toxicity and impaired reproduction. Adult largemouth bass (n=4 per treatment) were ip injected with a single dose of cadmium chloride (20 ug/kg) or a saline solution. After 48 hours, liver and testis were excised and differential gene expression profiles were examined.

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Effects of methoxychlor (MXC) in male largemouth bass

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