Toxicology Research
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2025
·Vol. 14
·期 1
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IF 2.1
Zhang Yan,Zhou Jin,Zhao Jianxin,Cheng Xiurong,Xing Caihong
In this study, we aimed to investigate the effects of chronic benzene exposure on the self-renewal capacity of C57BL/6 bone marrow HSPCs. Twenty-four male C57BL/6 mice were randomly divided into two groups: the control group and the benzene-exposed group. Mice in the benzene-exposed group inhaled 1,000 mg/m3 (308 ppm; conversion factor: 20 °C, 101 kPa, 1 ppm = 3.25 mg/m3) benzene for 32 weeks and the control group mice inhaled clean air. The peripheral blood hematological alterations were monitored every two weeks. Competitive bone marrow transplantation was performed to assess the self-renewal capacity of bone marrow HSPCs and the donor cell chimerism was quantified through flow cytometry. By the fourth week of benzene exposure, significant reductions in leukocytes, erythrocytes, and hemoglobin levels (P < 0.05) were observed, suggesting the development of benzene poisoning in mice. In the B6.SJL recipient mice, the chimerism ratio of bone marrow cells from C57BL/6 donors exposed to benzene for 20 weeks significantly decreased after transplantation (16 weeks post-transplant: 52.58% ± 17.38% in controls vs. 3.89% ± 1.96% in the benzene group, P < 0.05). Furthermore, the chimerism ratio in recipients of 32-week benzene-exposed donors approached zero by week 84 post-transplant, suggesting a loss of self-renewal capacity in bone marrow HSPCs due to benzene exposure. The study concludes that bone marrow suppression and the diminished self-renewal ability of C57BL/6 bone marrow HSPCs may lead to bone marrow failure in mice, contributing to the potential occurrence of MDS.
研究领域:
毒理学
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血液学
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实验医学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
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2025
·
IF 2.9
Zhongming Ye,Qihao Huang,Haipeng Wu,Shimei Wang,Boxin Li,Minjuan Zeng,Tikeng Jiang,Biyan Ye,Yixian Wei,Lei Sun,Shaoying Wang,Yutao Zeng,Yuting Chen,Huanwen Tang
Benzene, a recognized carcinogen, is utilized in synthesizing various chemicals. Epidemiological studies have established a positive correlation between benzene exposure and increased incidences of abnormal menstruation and dysmenorrhea. This exposure might also pose risks to the fetal hematopoietic system. However, the precise molecular mechanisms underlying these effects are not fully understood. In this study, a chronic benzene exposure model was established through dynamic inhalation. We assessed the autophagy levels in mouse ovarian granulosa cells and human ovarian granulosa cells treated with 1,4-benzoquinone using molecular biology techniques such as qPCR, Western blot, and transmission electron microscopy (TEM), etc. The experimental results show that Benzene-exposed mice exhibited autophagy, a reduced number of ovarian granulosa cells, and vacuolar lesions in the fallopian tubes. Cell-based experiments demonstrated that benzene exposure significantly upregulated SNHG15 expression in human ovarian granulosa cells ( P < 0.05). The upregulation of SNHG15 enhanced FOXO3 expression via the miR-3143/FOXO3 axis, which in turn increased the transcription of autophagy-related proteins such as Atg5 ( P < 0.05), ultimately leading to excessive autophagy in granulosa cells and ovarian dysfunction. Benzene and its metabolite benzoquinone increase autophagy in ovarian granulosa cells. The lncRNA SNHG15 regulates this autophagy induced by benzene exposure through sponge-like binding to miR-3143/FOXO3, thus impairing ovarian function. Inhibiting SNHG15, miR-3143, and FOXO3 expression markedly reduced autophagy in granulosa cells and ameliorated ovarian dysfunction resulting from benzene exposure. These results suggest that the ceRNA axis involving SNHG15 may be a potential clinical therapeutic target.
研究领域:
毒理学
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分子生物学
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遗传学
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生殖生物学
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环境卫生
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产品关联
DOI
PubMed
高影响因子
Journal of Hazardous Materials Advances
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2025
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IF 7.7
Yanjun Liu,Zefei Yang,Jingyao Chen,Huiyuan Yang,Yujia He,Zhengju Lv,Junbo Wang,Jianbing Wang
Landfills are significant sources of fugitive benzene release, posing a threat to the health of occupational populations. In this study, long-term monitoring of both external and internal benzene occupational exposure was conducted at a municipal solid waste (MSW) landfill site. The annual average concentration of benzene exposure in the landfill was 0.78 ± 1.08 μg/m³, with a notable increase in autumn (1.40 ± 5.29 μg/m³). The internal biomarker level (urinary t, t-muconic acid) significantly increased post-shift for the occupational population (6.65 ± 50.75 mg/g cr) compared to pre-shift (5.32 ± 31.62 mg/g cr, p < 0.05), exceeding the American Conference of Government Industrial Hygienists (ACGIH) limit by 13 times (0.5 mg/g cr). Machine learning models, particularly the Support Vector Regression (SVR) algorithm, outperformed traditional methods (e.g., Michaelis-Menten) in predicting internal exposure (R² = 0.989, root mean square error = 0.085). Using the SVR model, the predicted internal benzene level under the occupational exposure limit (1.7 mg/m³) was 1.65 mg/g cr, exceeding the ACGIH limit by three-fold. These findings provide a novel framework for benzene exposure risk assessment and inform targeted landfill management strategies.
研究领域:
环境卫生
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毒理学
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机器学习
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产品关联
DOI
高影响因子
TOXICOLOGY
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2025
·
IF 4.6
Ziyan Liu,Jingyu Wang,Wei Zhang,Huiwen Kang,Danyang Huang,Ziyan Wang,Guangyu Jiang,Ai Gao
The continuous accumulation of senescent hematopoietic stem progenitors (HSPCs) contributes to hematopoietic damage. Benzene is a confirmed human carcinogen, and its damage to HSPCs is a key event in benzene poisoning. However, whether the environmental dose of benzene is involved in HSPC damage by inducing cellular senescence has not been reported. Here, male C57BL/6 J mice were exposed to benzene vapour for 12 weeks (0, 10, 50 ppm), and mouse hematopoietic progenitor cell line FDC-P1 was exposed to benzene metabolite 1,4-BQ for 24 h (0, 5, 10 μM). In vivo and in vitro models combined with single-cell RNA sequencing have shown that benzene and its metabolites caused senescence in whole bone marrow and hematopoietic progenitor cells. Proteomics showed that benzene exposure significantly up-regulated interferon regulatory factor 4 (Irf4) in the bone marrow. Irf4 inhibition alleviated cellular senescence and hematopoietic damage, suggesting that Irf4 is a key molecule in benzene-induced hematopoietic cell senescence. Mechanistically, benzene caused a decrease in branched-chain amino acids (BCAAs) in whole bone marrow, hematopoietic progenitor cells, and plasma, and an increase in the BCAA catabolic enzyme Bcat1, mitochondrial ROS, and Bckdh activity. Irf4 inhibition down-regulated Bcat1, alleviated mitochondrial oxidative stress-dependent Bckdh abnormality, and up-regulated BCAAs. BCAA supplementation effectively alleviated benzene-induced cellular senescence and hematopoietic damage. In conclusion, the study identified that Irf4 triggered benzene-induced hematopoietic progenitor cell senescence and hematopoietic damage by mitochondrial injury-induced excessive BCAA catabolism. This study provides new ideas on the molecular mechanism of benzene-induced hematopoietic damage from the perspective of metabolism and senescence.
研究领域:
毒理学
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血液学
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分子生物学
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环境卫生
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代谢
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2017
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IF 4.95
Yaran Du,Xiqian Li,Haijiao Zheng,Xueju Lv,Qiong Jia
In the present work, a novel metal-organic framework (MOF) fluorescent probe was prepared by post-synthetic modification of MIL-53-NH 2 (Al) with carboxylatocalix[4]arene (CC[4]A). The introduced CC[4]A could not only enhance the fluorescence performance and the recognition ability of the probe, but also sustain the high stability under UV light and moisture conditions. A method based on the as-synthesized CC[4]A@MIL-53-NH 2 (Al) probe was established for sensing hippuric acid . The detection limit was determined to be as low as 3.7 μg mL −1 . Over the concentration range of 0.005–3 mg mL −1 , the calibration curve was obtained with a satisfactory linearity ( R 2 = 0.993). The method was successfully used for rapid and highly selective direct monitor of hippuric acid in human urine. The sensor had great potential to be used as a simple diagnostic tool for hippuric acid in human urine which is regarded as a biological index of toluene exposure.
研究领域:
化学
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材料科学
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分析化学
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环境科学
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产品关联
DOI
PubMed
高影响因子
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