Man-made mineral fiber effects on the expression of anti-oncogenes P53 and P16 and oncogenes C-JUN and C-FOS in the lung tissue of Wistar rats

Our plain-English summary of Man-made mineral fiber effects on the expression of anti-oncogenes P53 and P16 and oncogenes C-JUN and C-FOS in the lung tissue of Wistar rats, by Y. Cui, L. Huang, T. Huo, et al (Toxicology and Industrial Health, 2019).

The study

• Authors: Y. Cui, L. Huang, T. Huo, F. Dong, G. Wang, Q. Zhang
• Journal: Toxicology and Industrial Health
• Published: 2019;35(6):431-444
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Man-made mineral fibers (MMMFs) are substitutes for asbestos. MMMFs are widely used as insulation, but their molecular mechanisms underlying the tumorigenic effects in vivo have been poorly studied. For this reason, this work aimed to explore the properties and carcinogenic molecular mechanisms of MMMFs. The three MMMFs, rock wool (RW), glass fibers (GFs), and ceramic fibers (CFs), were prepared into respirable dust. Particle size, morphology, and chemical composition were analyzed by laser particle analyzer, scanning electron microscope, and X-ray fluorescence spectrometer, respectively. The Wistar rats were administered multiple intratracheal instillations of three MMMFs once a month. Then, several parameters (e.g. body mass, lung mass, and lung histology) were measured at 1, 3, and 6 months. After that, levels of P53, P16, C-JUN, and C-FOS mRNA and protein were measured by quantitative real-time reverse transcription polymerase chain reaction and Western blotting. This work found that exposure to MMMFs could influence the growth of body mass and increase lung mass. General conditions showed white nodules and irregular atrophy. In addition, MMMFs could lead to inactivation of anti-oncogene P16 and activation of proto-oncogenes (C-JUN and C-FOS) in the mRNA and protein levels, in which GF and CF were more obvious compared with RW. The effect of MMMFs was different, which may be related to the physical and chemical characteristics of different MMMFs. In conclusion, MMMFs (GF and CF) could induce an unbalanced expression of cancer-related genes in the lung tissues of rats. The understanding of the determinants of toxicity and carcinogenicity provides a scientific basis for developing and introducing new safer MMMF products, and the present study provides some useful insights into the carcinogenic mechanism of MMMFs.

In plain English

This rat experiment in China tested three man-made mineral fibers described as asbestos substitutes: rock wool, glass fibers and ceramic fibers. Seventy-two male Wistar rats were split into four groups, with six per group killed at 1, 3 and 6 months. Three groups received 0.5 ml of fiber suspension (2 mg/ml) into the windpipe monthly; controls received saline. Exposed rats weighed less than controls at 3 and 6 months; glass and ceramic fiber groups had heavier lungs. By 6 months, all exposed groups showed lung damage including fibrosis, most evident with glass and ceramic fibers. At 1 month, p16 mRNA was significantly above controls in all exposed groups, and P16 protein in the glass and ceramic fiber groups. By 6 months, both were below control levels in all exposed groups. C-JUN and C-FOS exceeded control levels at 3 and 6 months. P53 was higher at 1 and 3 months, but its protein did not differ at 6 months. The authors suggested the toxic effects may relate to reduced P16 and increased C-JUN and C-FOS, more obvious with glass and ceramic fibers than rock wool.

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 (fiber suspension placed into the windpipe) in rats, compared with a saline control group
• Who was studied: 72 male, 10-week-old, specific pathogen-free Wistar rats (180 to 200 g) from Southwest Medical University, China. They were randomly divided into four groups (control, rock wool, glass fiber, ceramic fiber), and six rats per group were killed at 1, 3 or 6 months.
• Exposure: Rock wool (RW), glass fibers (GF) and ceramic fibers (CF), ground into respirable dust. Each dose was 0.5 ml of a 2 mg/ml suspension in physiological saline, given once a month. The control group (NC) received saline.
• Main results:
  • Body mass of rats in each exposed group was lower than in the control group after 3 and 6 months (p less than 0.05)
  • Lung mass in the glass fiber and ceramic fiber groups was greater than in the control group at 3 and 6 months (p less than 0.05)
  • No rats became ill or died of natural causes during exposure. At 6 months, rats in all exposed groups ate, drank and moved less.
  • After 6 months, microscopic examination showed extensive fibrosis and alveolar damage in all exposed groups, most evident in the glass fiber and ceramic fiber groups
  • P53 mRNA and protein were significantly higher than in controls in the exposed groups at 1 and 3 months. At 6 months there was no difference in P53 protein between groups.
  • At 1 month, p16 mRNA was significantly higher than in controls in all three exposed groups. P16 protein was reported as significantly higher than in controls in the glass fiber and ceramic fiber groups; the article reports no significant protein increase for rock wool.
  • At 6 months, P16 mRNA and protein were significantly lower than in controls in all exposed groups, with protein levels ranked rock wool, then glass fiber, then ceramic fiber (highest to lowest)
  • At 3 and 6 months, C-JUN mRNA and protein were significantly higher than in controls in each exposed group. c-jun mRNA was lower in the rock wool group than in the glass and ceramic fiber groups.
  • At 3 and 6 months, C-FOS mRNA and protein were significantly higher than in controls in each exposed group. At 6 months the rock wool group had significantly lower levels than the other exposed groups.
  • Average particle sizes were 14.99 (rock wool), 1.85 (glass fiber) and 5.77 (ceramic fiber). The scan prints the unit as "mm", which, given the article's statement that these met respirable dust requirements, is most likely a scanning error for micrometres.
• The authors' conclusion: The authors concluded that it is reasonable to suggest the toxic effects of these man-made mineral fibers may be related to inactivation of the p16 gene and activation of c-jun and c-fos. They also concluded that glass fiber and ceramic fiber had more obvious effects on these cancer-related genes than rock wool.
• Limitations the authors state:
  • The results cannot be directly compared with inhalation and biopersistence experiments, because the way fibers were given and the calculation of clearance half-time differed from earlier studies
  • The authors called for further study of related pathways and of fiber changes in the body after long-term exposure

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Carcinogenic, Histology.

Related studies

• Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats' lung tissues — Y. Cui, Y. Wang, et al. (2018)
• Lung injury and expression of p53 and p16 in Wistar rats induced by respirable chrysotile fiber dust from four primary areas of China — Y. Zeng, Y. Cui, et al. (2018)
• Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile — Y. Cui, Y. Zha, et al. (2019)
• Long-term instillation to four natural representative chrysotile of China induce the inactivation of P53 and P16 and the activation of C-JUN and C-FOS in the lung tissues of Wistar rats — Y. Luo, J. Deng, et al. (2020)
• p53, Cip1, and Gadd153 expression following treatment of A549 cells with natural and man-made vitreous fibers — N.F. Johnson, R.J. Jaramillo (1997)
• Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats — J. Topinka, P. Loli, et al. (2006)

Browse more research in Toxicology and Industrial Health, or return to medical research.