|Alternative Title||The toxicity and mechanism of typical benzophenones to fish|
|Thesis Advisor||王子健 ; 查金苗|
|Place of Conferral||北京|
|Keyword||苯甲酮类物质,繁殖毒性,遗传毒性,稀有鮈鲫,Rna-seq Benzophenones, Chinese Rare Minnow, Japanese Medaka, Reproduction, Genetic Toxicity, Rna-seq|
Based on the good ability of UV absorption, benzophenone-type UV filters (BPs) have been added to various personal care products and the maximum amount of benzophenones added in personal care products can be up to 10%. BPs have been detected frequently in water environments due to their increased consumption. Although BPs have relatively low risks and toxicity on human health, they are potential pseudo-pseudopersistence and bioconcentration. Therefore, BPs were selected to be the research object. In order to study their toxic and toxicological mechanisms to fish, the non-target organisms, Japanese medaka (Oryzias latipes) and Chinese rare minnow (Gobiocypris rarus) were used to carry out the experiment, providing basic data and technical support for the management on environmental risks of BPs. Based on the combination of short-term and long-term exposure experiments, the following innovative results were obtained:
The results of short-term reproduction and reproduction of Japanese medaka showed that BP, BP-4, BP-12, BZD, and 2,3,4-triOH-BP significantly changed total oviposition of medaka. In the clean water experiment, BPs increased the cumulative mortality and malformation rate of offspring (p<0.05), and in the continued exposure experiment, BPs significantly decreased the hatching rate, increased the mortality rate and the total deformity rate (p<0.05). BP, BP-2, BP-3, BP-4, 4-OH-BP, and 2,3,4-triOH-BP significantly increased levels of VTG in the plasma of males (p<0.05); BP, BP-1, BP-2, BP-4, and BP-12 significantly increased the mRNA expression of fshβ and lhβ in the brain of medaka (p<0.05). BP, BZD and 4-OHBP significantly increased the mRNA expression of fshr and lhr in the gonads of females (p<0.05). BP, BP-2, BP-4, BP-12, BZD, and 2,3,4-triOHBP significantly increased the levels of lhr gene in gonads of males. BP, BP-1, BP-4, and BP-12 caused a significant increase in cyp19β mRNA expression in the brains of females (p<0.05), while BP, BZD, and 2,3,4-triOH-BP increased the mRNA expression ofcyp19β in male fish brain (p<0.05), The results of the histological analysis showed that mature oocytes had significantly reduced, while immature oocytes were increased significantly, and degenerating oocytes appeared. The proportion of mature sperm in testes were also significant decreased. The results show that BPs not only have reproductive and developmental toxicity, but also have endocrine disrupting effects；The results confirmed that the reproductive activity of BPs is related to the substituents. The more hydroxyl groups, the higher the effect; one methoxy group has the same effect as one hydroxyl group; the sulfonic acid group increases the effect; the metabolite effect is obviously increased compared with the parent compound.
The long-term exposure experiments of medaka show that BP, BP-1, and BP-4 have reproductive toxicity, changed the hatching rate of offspring, increased mortality and deformity rate, significant increase the levels of VTG and E2, and changed mRNA expression of HPG axis-related genes. Histological analysis confirmed that the three benzophenones inhibit the formation of mature sperm in the male glands and mature oocytes in female glands. According to the above endpoints, the long-term low-dose BP, BP-1 and BP-4 exposures not only affect reproduction, growth and development, but also show highter estrogen-like activity.
The short-term test of Chinese rare minnow confirmed that BP, BP-1, and BP-4 at the transcriptome level altered DNA damage-related signaling pathways such as cell cycle, DNA repair, and apoptosis. BP, BP-1 and BP-4 can induce DNA damage, activate and 8-OHdG, and increase the caspase activity and apoptosis rate. These results suggest that BP, BP-1 and BP-4 have genotoxicity. Their genotoxicity mechanism was that BP, BP-1 and BP-4 caused oxidative DNA damage in the livers of males, further inhibited DNA repair, causing cell cycle arrest, and lead to apoptosis.
|闫赛红. 典型苯甲酮类物质对鱼类的毒性与毒理机制研究[D]. 北京. 中国科学院生态环境研究中心,2018.|
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