Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats’ lung tissues
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.
KeywordsChrysotile Cancer P53 P16 C-jun C-fos
This research was funded by the Key Program of National Nature Science Project of China (No. 41130746), the National Natural Fund Project of China (No. 41472046), and the Department of Sichuan Province Natural Science Foundation of China (14JC0126).
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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