Lung injury and expression of p53 and p16 in Wistar rats induced by respirable chrysotile fiber dust from four primary areas of China

Our plain-English summary of Lung injury and expression of p53 and p16 in Wistar rats induced by respirable chrysotile fiber dust from four primary areas of China, by Y. Zeng, Y. Cui, J. Ma, et al (Environmental Science and Pollution Research International, 2018).

The study

• Authors: Y. Zeng, Y. Cui, J. Ma, T. Huo, F. Dong, Q. Zhang, J. Deng, X. Zhang, J. Yang, Y. Wang
• Journal: Environmental Science and Pollution Research International
• Published: 2018;25(23):22389-22399
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chrysotile products were widely used in daily life, and a large amount of respirable dust was produced in the process of production and application. At present, there was seldom research on the safety of chrysotile fiber dust, and whether its long-term inhalation can lead to lung cancer was unknown. In order to determine whether respirable chrysotile fiber dust of China caused lung cancer, four major chrysotile-producing mine areas in China were selected for this study. Chrysotile fibers were prepared into respirable dust. Particle size was measured by laser particle analysis, morphology was observed by scanning electron microscope, chrysotile fiber phase was analyzed by X-ray diffraction, trace chemical elements were identified by X-ray fluorescence, and the structure and the active groups of the dust were determined after grinding by Fourier transform infrared spectroscopy. Male Wistar rats were exposed to non-exposed intratracheal instillation with different concentrations of chrysotile fiber dust. The rats were weighed after 1, 3, and 6 months, then the lung tissues were separated, the lung morphology was observed, and the pulmonary index was calculated. Pathological changes in lung tissues were observed by optical microscope after the HE staining of tissues, and the gene expression of p53 and p16 was determined by reverse transcription polymerase chain reaction. First, the results showed that the particle sizes of the four fibers were less than 10 μm. Four primary areas of chrysotile had similar fibrous structure, arranged in fascicles, or mixed with thin chunks of material. Second, the elementary composition of the four fibers was mainly chrysotile, and the structure and the active groups of the grinding dust were not damaged. Third, the weights of the treated rats were obviously lower, and the lung weights and the pulmonary index increased significantly (P < 0.05). Fourth, the treated Wistar rat lung tissues revealed different degrees of congestion, edema, inflammatory cell infiltration, and mild fibrosis. Fifth, the p53 and p16 genes decreased in the Mangnai group after 1 month of exposure, and the other groups increased. The expression of p53 and p16 in each group decreased significantly after 6 months (P < 0.05). In conclusion, the respirable chrysotile fiber dust from the four primary areas of China had the risk of causing lung injury, and these changes may be related to the physical and chemical characteristics of chrysotile from different production areas.

In plain English

In this animal experiment, the authors ground chrysotile from four Chinese mining areas (Mangnai, Aksai, Southern Shanxi and Xinkang) into respirable dust. They instilled it into the windpipes of male Wistar rats once a month at 0.5 to 8.0 mg per mL. Negative control rats received saline. Lungs were examined at 1, 3 and 6 months. Exposed lungs showed congestion and inflammatory cell infiltration and, with longer treatment, consolidation and fibrosis. No visible tumors were seen. Pulmonary index (lung weight relative to body weight) did not differ significantly from controls at 1 month. At 6 months, the article's table marks Xinkang (0.55), Mangnai (0.43) and Aksai (0.34) rats as significantly above controls (0.28). In rats given 2.0 mg per mL, p16 gene expression was significantly lower than in controls at 3 and 6 months. p53 expression was significantly lower at 6 months but not at 3 months. The authors concluded that the dust damaged rat lungs to different degrees and had an associated risk of causing lung cancer, possibly related to its physical and chemical characteristics.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: repeated intratracheal instillation of chrysotile dust in rats, with laboratory analysis of the dust's size, shape and chemistry
• Who was studied: Male Wistar rats aged 8 to 10 weeks from the Laboratory Animal Center, West China Medical College, Sichuan University. The article states 90 rats in seven groups (five dose groups, a negative control and a positive control) and also says each group had 18 rats.
• Exposure: Respirable chrysotile dust from four Chinese mining areas: Mangnai (Qinghai), Aksai (Gansu), Southern Shanxi (Shanxi) and Xinkang (Sichuan). Doses were 0.5, 1.0, 2.0, 4.0 and 8.0 mg per mL, given as 0.5 mL once a month. The positive control was benzopyrene in corn oil and the negative control was saline. p53 and p16 were measured in rats given 2.0 mg per mL.
• Main results:
  • After grinding, mean particle sizes were 4.26 μm (Aksai), 1.84 μm (Xinkang), 2.83 μm (Southern Shanxi) and 4.76 μm (Mangnai).
  • Mangnai and Aksai dust was mainly chrysotile. Southern Shanxi dust was chrysotile and brucite. Xinkang dust was chrysotile and some quartz.
  • Exposed lungs showed congestion and surface changes that increased over time. No visible neoplasias (tumors) were seen in exposed lung tissue.
  • On microscopy, lung disease in each exposed group worsened with longer treatment, including consolidation and fibrosis. Aksai dust mainly caused bleeding and inflammatory cell infiltration. Mangnai dust mainly caused inflammatory cell infiltration and mild alveolar changes. Southern Shanxi and Xinkang dust mainly caused lung compartment enlargement and inflammatory cell infiltration around the bronchi.
  • Pulmonary index did not differ significantly from negative controls at 1 month. In the table, the 6-month pulmonary index was 0.28 ± 0.02 in negative controls, 0.55 ± 0.02 in Xinkang rats, 0.43 ± 0.03 in Mangnai rats and 0.34 ± 0.02 in Aksai rats, each marked significant (P < 0.05). Southern Shanxi rats were 0.33 ± 0.04, not marked significant. The authors ranked the pulmonary index from highest to lowest as Xinkang, Mangnai, Aksai, Southern Shanxi.
  • Compared with negative controls, p53 expression in exposed rat lungs was not significantly different at 3 months.
  • Compared with negative controls, p53 expression in exposed rat lungs was significantly lower at 6 months (P < 0.05).
  • Compared with negative controls, p16 expression in exposed rat lungs was significantly lower at 3 and 6 months (P < 0.05). The decrease was greatest with Mangnai dust, followed by Aksai, Xinkang and Southern Shanxi.
• The authors' conclusion: The authors concluded that respirable chrysotile dust from the four areas damaged rat lung tissue to different extents, with long-term exposure causing fibrosis, Xinkang dust causing the most damage and Southern Shanxi the least. They concluded that it lowered p53 and p16 expression and had an associated risk of causing lung cancer, and that these effects may be related to the dust's physical and chemical characteristics.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Lung Cancer, X-Ray Diffraction (XRD), Infrared Spectroscopy (IR), Fibrosis.

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