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

Interface Effect of Ultrafine Mineral Particles and Microorganisms

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.

Keywords

Chrysotile Cancer P53 P16 C-jun C-fos 

Notes

Compliance with ethical standards

Procedures involving the rats and their care were approved by the Ethics Committee of Animal Care and Experimentation of Southwest Medical University and have been conducted in accordance with Chinese National Guidelines for the Care and Use of Laboratory Animal in animal experiments.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.School of Public HealthSouthwest Medical UniversityLuzhouPeople’s Republic of China
  2. 2.Department of Clinical Laboratory404 Hospital of MianyangMianyangPeople’s Republic of China
  3. 3.Key Laboratory of Solid Waste Treatment and the Resource RecycleSouthwest University of Science and TechnologyMianyangPeople’s Republic of China

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