| Polychlorinated biphenyl is a kind of persistent organic pollutants,which has been banned for many years,but still be widely distributed in the environment.PCBs are highly hydrophobic and lipophilic,and get in the body through environmental expose and food chain.There is a positive correlation between the burden in different tissues and the fat content of the tissue.Those who has the higher fat content in tissue,adipose or liver,accumulate more PCBs.That's why fat mobilization can lead to changes in the distribution of PCBs.There are many studies on the toxic effects of PCBs,which mainly focus on the effects of mixed function oxidase system,biological antioxidant defense,chemical carcinogenesis and so on.In this stuty,we used zebrafish as the experimental animal and PCBs as a typical POPs.1.We feed zebrafish in different conditions,which were 2%per day and feed until be full.Significent different fat content was found after 14-days-feed.The fat content was stable in day35,which was 1.18 times(?)and 1.28 times((?))as much as in control group.In addition,there was no significant change in the body length during the modeling processing.It was proved that the model of differect body fat content was established.2.In the exposure stage,high fat and low fat group of zebrafish were exposed to 10 ?g/L PCBs for 14 days,and then transferred into freshwater for 21 days.In each sampling point,liver lipid metabolism gene(PPAR alpha)had a fluctuating expression,and fat content did not change significantly,liver histology demonstrated no difference under the experimental conditions.The results showed that PCBs has limited effects on fat mobilization.3.Exposure of 10 ?g/L PCBs induced the aryl hydrocarbon receptor(AhR),cytochrome P450 1a(CYP1a)(phase I metabolism related genes),and glutathione S-transferase(GST),UDP-glucuronosyltransferase(UGT)(phase II metabolism related genes),but the response was not the same in different groups with different fat contents.Low fat content group had the lower expression of those genes in both stages.It showed that individuals with lower body fat content were more strong in the metabolism of PCBs.4.Exposure of 10 ?g/L PCBs also induced heat shock protein 70(HSP70),nuclear factor related factor 2(Nrf2)(oxidative stress response genes)and protein kinase 38(p38),tumor protein 53(tp53)(carcinogenesis genes)(P<0.05),and different genes process different response.In summary,the expression in low fat content group was significantly higher than that in high fat content group(P<0.05)in the exposure stage,and decayed faster during the scavenging stage.The results showed that high body fat had protective effects on PCBs induced toxicity.5.In scavenging the stage,fasting conditions lead to up regulate the expression of the PPARa gene.The lipid droplets in liver cells disappeared,body fat content in 21d was significantly decreased by 44.1%(female)and 52%(male).Body fat mobilization induces a dramatic fluctuation in the expression of PCBs related genes,indicating that PCBs release and metabolism rates during body fat mobilization were not linearly related to body fat loss.Body fat mobilization may also lead to changes in the expression of toxic biomarkers such as oxidative stress and carcinogenesis.The response of different genes to exposure was different and had gender differences.It also showed that zebrafish during body fat mobilization were more strongly affected by PCBs toxicity.Conclusion:Stationary high fat content has a protective effect on the oxidative stress and carcinogenesis induced by PCB exposure in both exposure and scavenging stage.However,the metabolism of body fat can lead to the change of biomarker responses,indicating that the body may be experiencing a new round of endogenous PCBs exposure.The results of this study not only enrich the toxicological theory related to POPs,but also contribute to the formulation and results analysis of the relevant toxicological evaluation. |
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