Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats' lung tissues

Our plain-English summary of Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats' lung tissues, by Y. Cui, Y. Wang, J. Deng, et al (Environmental Science and Pollution Research International, 2018).

The study

• Authors: Y. Cui, Y. Wang, J. Deng, G. Hu, F. Dong, Q. Zhang
• Journal: Environmental Science and Pollution Research International
• Published: 2018;25(23):22378-22388
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chrysotile is the most widely used form of asbestos worldwide. China is the world's largest consumer and second largest producer of chrysotile. The carcinogenicity of chrysotile has been extensively documented, and accumulative evidence has shown that chrysotile is capable of causing lung cancer and other forms of cancer. However, molecular mechanisms underlying the tumorigenic effects of chrysotile remained poorly understood. To explore the carcinogenicity of chrysotile, Wistar rats were administered by intratracheal instillation (by an artificial route of administration) for 0, 0.5, 2, or 8 mg/ml of natural chrysotile (from Mangnai, Qinghai, China) dissolved in saline, repeated once a month for 6 months (a repeated high-dose exposure which may have little bearing on the effects following human exposure). The lung tissues were analyzed for viscera coefficients and histopathological alterations. Expression of P53, P16, C-JUN, and C-FOS was measured by western blotting and qRT-PCR. Our results found that chrysotile exposure leads the body weight to grow slowly and lung viscera coefficients to increase in a dose-dependent manner. General sample showed white nodules, punctiform asbestos spots, and irregular atrophy; moreover, HE staining revealed inflammatory infiltration, damage of alveolar structures, agglomerations, and pulmonary fibrosis. In addition, chrysotile can induce inactivation of the anti-oncogene P53 and P16 and activation of the proto-oncogenes C-JUN and C-FOS both in the messenger RNA and protein level. In conclusion, chrysotile induced an imbalanced expression of cancer-related genes in rats' lung tissue. These results contribute to our understanding of the carcinogenic mechanism of chrysotile.

In plain English

The authors studied 36 male Wistar rats; 27 received natural chrysotile from Mangnai, Qinghai, China, in which no amphibole was detected. The rats formed four groups of nine, including a saline control; three per group were killed at 1, 3 and 6 months. Monthly, each rat received 0.5 ml of saline containing 0, 0.5, 2 or 8 mg/ml chrysotile, instilled into the windpipe. From 2 months, the 2 and 8 mg/ml groups weighed significantly less than controls. They also had heavier lungs relative to body weight than controls and the 0.5 mg/ml group. At 1 month, 8 mg/ml lungs had white nodules; at 3 months, both groups showed asbestos spots and damaged air sacs; at 6 months, both showed fibrosis. Exposed groups had lower P53 protein than controls at 3 and 6 months. P16 rose at 1 month but fell at 3 months. C-JUN and C-FOS rose. The authors concluded it is reasonable to assume chrysotile inactivates the anti-oncogenes P53 and P16 and activates the proto-oncogenes C-JUN and C-FOS. They noted these repeated high doses may have little bearing on human exposure.

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 (rats dosed with chrysotile by intratracheal instillation, compared with a saline negative control group)
• Who was studied: 36 specific pathogen-free male Wistar rats, 10 weeks old, randomly divided into four groups of nine: one normal saline negative control group and three chrysotile groups. Three rats per group were killed at 1, 3 and 6 months after the first dose (China, Southwest Medical University)
• Exposure: natural chrysotile from Mangnai, Qinghai, China (no amphibole detected by X-ray diffraction, detection limit 0.01–0.05%), suspended in saline at 0, 0.5, 2 or 8 mg/ml; 0.5 ml given by intratracheal instillation once a month; penicillin sodium was added to both control and chrysotile preparations
• Main results:
  • From 2 months on, body weights of the 2 and 8 mg/ml groups were significantly lower than those of the 0.5 mg/ml group and the negative control (p less than 0.05)
  • Lung viscera coefficients (lung weight relative to body weight) of the 2 and 8 mg/ml groups were higher than those of the negative control and the 0.5 mg/ml group (p less than 0.05)
  • At 1 month, the lung surfaces of the 8 mg/ml group had white nodules
  • At 3 months, the lung surfaces of the 2 and 8 mg/ml groups showed punctiform asbestos spots, and microscopy showed damaged alveolar structures
  • At 6 months, microscopy showed atrophied alveoli, agglomerations and fibrosis in both the 2 and 8 mg/ml groups
  • P53 protein levels at 3 and 6 months in the chrysotile-exposed groups decreased compared with the negative control (described as significant and dose-dependent)
  • At 1 month, P16 protein and mRNA in the chrysotile-exposed groups were significantly higher than in the negative control
  • At 3 months, P16 protein and mRNA in the chrysotile-exposed groups were significantly lower than in the negative control, in a dose-dependent way
  • At 3 months, C-JUN protein in the chrysotile-exposed groups was significantly higher than in the negative control, in a dose-dependent way
  • Overall, chrysotile increased the protein and mRNA levels of C-JUN and C-FOS in the rat lung
• The authors' conclusion: The authors concluded it is reasonable to assume that chrysotile induces inactivation of the anti-oncogenes P53 and P16 and activation of the proto-oncogenes C-JUN and C-FOS at both the mRNA and protein level
• Limitations the authors state:
  • The repeated high-dose exposure may have little bearing on the effects of human exposure
  • Intratracheal instillation is an artificial route of administration

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, Pulmonary Fibrosis, Carcinogenic.

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