Advertisement

Environmental Science and Pollution Research

, Volume 25, Issue 23, pp 22389–22399 | Cite as

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

  • Yali Zeng
  • Yan Cui
  • Ji Ma
  • Tingting Huo
  • Faqin Dong
  • Qingbi Zhang
  • Jianjun Deng
  • Xu Zhang
  • Jie Yang
  • Yulin Wang
Interface Effect of Ultrafine Mineral Particles and Microorganisms

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.

Keywords

Respirable dust Antioncogene p53 p16 Chrysotile Pulmonary index 

Abbreviations

AKS

Aksai

DNA

Deoxyribonucleic acid

FTIR

Fourier transform infrared spectroscopy

HE

Hematoxylin and eosin

MN

Mangnai

PI

Pulmonary index

RNA

Ribonucleic acid

RT-PCR

Reverse transcription polymerase chain reaction

SEM

Scanning electron microscope

SSX

Southern Shanxi

XK

Xinkang

XRD

X-ray diffraction

XRF

X-ray fluorescence

Notes

Funding

This research was funded by the National Natural Fund Project of China (No. 41472046), the Key Program of the National Natural Science Project of China (No. 41130746), the Science and Technology Project of Sichuan Province, China (No. 2016JY0045), and the Department of Sichuan Province Natural Science Foundation of China (No. 14JC0126).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. Akatsuka S, Toyokuni S (2016) Iron function and carcinogenesis. Nihon Rinsho 74:1168–1175Google Scholar
  2. Al-Hallak MH, Sarfraz MK, Azarmi S, Roa WH, Finlay WH, Rouleau C et al (2012) Distribution of effervescent respirable nanoparticles after pulmonary delivery: an in vivo study. Ther Deliv 3(6):725–734CrossRefGoogle Scholar
  3. Barbieri PG, Somigliana A, Girelli R, Lombardi S, Sarnico M, Silvestri S (2016) Pleural mesothelioma in a school teacher, asbestos exposure due to DAS paste. Med Lav 107:141–147Google Scholar
  4. Baur X, Soskolne CL, Lemen RA, Schneider J, Woitowitz HJ, Budnik LT (2015) How conflicted authors undermine the World Health Organization (WHO) campaign to stop all use of asbestos, spotlight on studies showing that chrysotile is carcinogenic and facilitates other non-cancer asbestos-related diseases. Int J Occup Environ Health 21:176–179CrossRefGoogle Scholar
  5. Bernstein D, Dunnigan J, Hesterberg T, Brown R, Velasco JA, Barrera R, Hoskins J, Gibbs A (2013) Health risk of chrysotile revisited. Crit Rev Toxicol 43:154–183CrossRefGoogle Scholar
  6. Browning CL, Qin Q, Kelly DF, Prakash R, Vanoli F, Jasin M, Wise JP Sr (2016) Prolonged particulate hexavalent chromium exposure suppresses homologous recombination repair in human lung cells. Toxicol Sci 153:70–78CrossRefGoogle Scholar
  7. Burmeister B, Schwerdtle T, Poser I, Hoffmann E, Hartwig A, Müller WU, Rettenmeier AW, Seemayer NH, Dopp E (2004) Effects of asbestos on initiation of on initiation of DNA damage, induction of DNA-strand breaks, P53-expression and apoptosis in primary, SV40-transformed and malignant human mesothelial cells. Mutat Res 558:81–92CrossRefGoogle Scholar
  8. Cao H, Gao F, Xia B, Xiao Q, Guo X, Hu G, Zhang C (2016) The co-induced effects of molybdenum and cadmium on the mRNA expression of inflammatory cytokines and trace element contents in duck kidneys. Ecotoxicol Environ Saf 133:157–163CrossRefGoogle Scholar
  9. Chen D, Mei L, Zhou Y, Shen C, Huan XU, Niu Z et al (2015) A novel differential diagnostic model for multiple primary lung cancer: differentially-expressed gene analysis of multiple primary lung cancer and intrapulmonary metastasis. Oncol Lett 9(3):1081–1088CrossRefGoogle Scholar
  10. Chiou YH, Liou SH, Wong RH, Chen CY, Lee H (2015) Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancervia nickel-induced microRNA-21 expression. Toxicol Lett 237: 46–54Google Scholar
  11. Choi S, Suk MH, Paik NW (2010) Asbestos-containing materials and airborne asbestos levels in industrial buildings in korea. J Uoeh 32(1):31–43CrossRefGoogle Scholar
  12. Courtice MN, Wang X, Lin S, Yu IT, Berman DW, Yano E (2016) Exposure-response estimate for lung cancer and asbestosis in a predominantly chrysotile-exposed Chinese factory cohort. Am J Ind Med 59:369–378CrossRefGoogle Scholar
  13. Dahlgren J, Talbott P (2015) Case report, peritoneal mesothelioma from asbestos in hairdryers. Int J Occup Environ Health 21:1–4CrossRefGoogle Scholar
  14. Daniel D, Pengcheng X, Kuninobu Y, Emily W, Ka H, Joshaghani H, Mirkarimi HS, Besharat S, Roshandel G, Sanaei O, Nejabat M (2015) Magnesium intake and incidence of pancreatic cancer: the VITamins and Lifestyle study. Br J Cancer 113:1615–1621CrossRefGoogle Scholar
  15. Darne C, Coulais C, Terzetti F, Fontana C, Binet S, Gaté L, Guichard Y (2016) In vitro comet and micronucleus assays do not predict morphological transforming effects of silica particles in Syrian hamster embryo ccells. Mutat Res Genet Toxicol Environ Mutagen 796:23–33CrossRefGoogle Scholar
  16. Demirhan O, Taştemir D, Hastürk S, Kuleci S, Hanta I (2010) Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: fluorescence in situ hybridization and cytogenetic studies. Cancer Epidemiol 34:472–477CrossRefGoogle Scholar
  17. Egilman D, Bird T (2016) Short fiber tremolite free chrysotile mesothelioma cohort revealed. Am J Ind Med 59(3):196–199CrossRefGoogle Scholar
  18. Fan X, Yu K, Wu J, Shao J, Zhu L, Zhang J (2014) Correlation between squamous cell carcinoma of the lung and human papillomavirus infection and the relationship to expression of p53 and p16. Tumour Biol 36:3043–3049CrossRefGoogle Scholar
  19. Gao Z, Hiroshima K, Wu X, Zhang J, Shao D, Shao H, Yang H, Yusa T, Kiyokawa T, Kobayashi M, Shinohara Y, Røe OD, Zhang X, Morinaga K (2015) Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women, analysis of 28 cases in Southeast China. Am J Ind Med 58:1040–1049CrossRefGoogle Scholar
  20. Gao J, Woodward A, Vardoulakis S, Kovats S, Wilkinson P, Li L, Xu L, Li, Yang J, Li J, Cao L, Liu X, Wu H, Liu Q (2017) Haze, public health and mitigation measures in China, a review of the current evidence for further policy response. Sci Total Environ 578:148–157CrossRefGoogle Scholar
  21. Gilham C, Rake C, Burdett G, Nicholson AG, Davison L, Franchini A, Carpenter J, Hodgson J, Darnton A, Peto J (2016) Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden. Occup Environ Med 73:290–299CrossRefGoogle Scholar
  22. Guan WJ, Zheng XY, Chung KF, Zhong NS (2016) Impact of air pollution on the burden of chronic respiratory diseases in China, time for urgent action. Lancet 388:1939–1951CrossRefGoogle Scholar
  23. Halasova E, Matakova T, Skerenova M, Krutakova M, Slovakova P, Dzian A, Javorkova S, Pec M, Kypusova K, Hamzik J (2016) Polymorphisms of selected DNA repair genes and lung cancer in chromium exposure. Adv Exp Med Biol 911:17–22CrossRefGoogle Scholar
  24. Hamra GB, Richardson DB, Dement J, Loomis D (2017) Lung cancer risk associated with regulated and unregulated chrysotile asbestos fibers. Epidemiology 28:275–280CrossRefGoogle Scholar
  25. Jiang L, Nagai H, Ohara H, Hara, Tachibana M, Hirano S, Shinohara Y, Kohyama N, Akatsuka S, Toyokuni S (2008) Characteristics and modifying factors of asbestos-induced oxidative DNA damage. Cancer Sci 99:2142–2151CrossRefGoogle Scholar
  26. Kim Y, Myong P, Lee JK (2015) CT characteristics of pleural plaques related to occupational or environmental asbestos exposure from South Korean asbestos mines. Korean J Radiol 16:1142–1152CrossRefGoogle Scholar
  27. Lappano R, Malaguarnera R, Belfiore A, Maggiolini M (2016) Recent advances on the stimulatory effects of metals in breast cancer. Mol Cell Endocrinol S0303-7207:30425–30427Google Scholar
  28. Lemaire I, Beaudoin H, Massé S, Grondin C (1986) Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis. Am J Pathol 122:205–211Google Scholar
  29. Li J, Du H, Wang Z, Sun Y, Yang W, Li J, Tang X, Fu P (2017) Rapid formation of a severe regional winter haze episode over a mega-city cluster on the North China Plain. Environ Pollut S0269-7491:30299–30303Google Scholar
  30. Mancuso TF (1997) Chromium as an industrial carcinogen, Part II. Chromium in human Tissues. Am JInd MED 31:140–147Google Scholar
  31. Marioryad H, Kakooei H, Shahtaheri SJ, Yunesian M, Azam K (2011) Assessment of airborne asbestos exposure at an asbestos cement sheet and pipe factory in Iran. Regul Toxicol Pharmacol 60:200–205CrossRefGoogle Scholar
  32. Matsuoka M, Igisu H, Morimoto Y (2003) Phosphorylation of p53 protein in A549 human pulmonary epithelial cells exposed to asbestos fibers. Environ Health Perspect 111:509–512CrossRefGoogle Scholar
  33. Mishra A, Liu JY, Brody AR, Morris GF (1997) Inhaled asbestos fibers p53 induce expression in the rat lung. Am J Respir Cell Mol Biol 16:479–485CrossRefGoogle Scholar
  34. Núñez O, Fernández-Navarro P, Martín-Méndez I, Bel-Lan A, Locutura JF, López-Abente G (2016) Arsenic and chromium topsoil levels and cancer mortality in Spain. Environ Sci Pollut Res Int 23:17664–17675CrossRefGoogle Scholar
  35. Pavela M, Uitti J, Pukkala E (2017) Cancer incidence among copper smelting and nickel refining workers in Finland. Am J Ind Med 60:87–95Google Scholar
  36. Piao CQ, Zhao YL, Hei TK (2001) Analysis of p16 and p21 (Cip1) expression in tumorigenic human bronchial epithelial cells induced by asbestos. Oncogene 20:7301–7306CrossRefGoogle Scholar
  37. Pollastri S, D'Acapito F, Trapananti A, Colantoni I, Andreozzi GB, Gualtieri AF (2015) The chemical environment of iron in mineral fibres. A combined X-ray absorption and Mössbauer spectroscopic study. J Hazard Mater 298:282–293CrossRefGoogle Scholar
  38. Pratheeshkumar P, Son YO, Divya SP, Turcios L, Roy RV, Hitron JA, Wang L, Kim D, Dai J, Asha P, Zhang Z, Shi X (2016) Hexavalent chromium induces malignant transformation of human lung bronchial epithelial cells via ROS-dependent activation of miR-21-PDCD4 signaling. Oncotarget 7:51193–51210CrossRefGoogle Scholar
  39. Salamatipour A, Mohanty SK, Pietrofesa A, Vann DR, Christofidou-Solomidou M, Willenbring JK (2016) Asbestos fiber preparation methods affect fiber toxicity. Environ Sci Technol Lett 3:270–274CrossRefGoogle Scholar
  40. Scarlett HP, Postlethwait E, Delzell E, Sathiakumar N, Oestenstad RK (2012) Asbestos in public hospitals, are employees at risk. Environ Health 74:22–26Google Scholar
  41. Scimeca M, Orlandi A, Terrenato I, Bischetti S, Bonanno E (2014) Assessment of metal contaminants in non-small cell lung cancer by EDX microanalysis. Eur J Histochem 58:2403CrossRefGoogle Scholar
  42. Sporn TA (2011) Mineralogy of asbestos. Recent Results Cancer Res 189:1–11CrossRefGoogle Scholar
  43. Stankovic T, Milinkovic V, Bankovic J, Dinic J, Tanic N, Dramicanin T, Tanic N (2014) Comparative analyses of individual and multiple alterations of p53, PTEN and p16 in non-small cell lung carcinoma, glioma and breast carcinoma samples. Biomed Pharmacother 68:521–526CrossRefGoogle Scholar
  44. Ono K, Sugio K, Uramoto H, Baba T, Ichiki Y, Takenoyama M et al (2009) Discrimination of multiple primary lung cancers from intrapulmonary metastasis based on the expression of four cancer-related proteins. Cancer 115(15):3489–3500CrossRefGoogle Scholar
  45. Tiwari R, David CM, Mahesh DR, Sambargi U, Rashmi KJ, Benakanal P (2016) Assessment of serum copper, iron and immune complexes in potentially malignant disorders and oral cancer. Braz Oral Res 30:e101CrossRefGoogle Scholar
  46. Tomioka K, Saeki K, Obayashi K, Kurumatani N (2016) Risk of lung cancer in workers exposed to benzidine and/or beta-naphthylamine: a systematic review and meta-analysis. J Epidemiol 26:447–458CrossRefGoogle Scholar
  47. Wang F, Ni SS, Liu H (2016) Pollutional haze and COPD, etiology, epidemiology, pathogenesis, pathology, biological markers and therapy. J Thorac Dis 8:E20–E30Google Scholar
  48. Xu W, Han T, Du W, Wang Q, Chen C, Zhao J, Zhang Y, Li J, Fu P, Wang Z, Worsnop DR, Sun Y (2017) Effects of aqueous-phase and photochemical processing on secondary organic aerosol formation and evolution in Beijing, China. Environ Sci Technol 51:762–770CrossRefGoogle Scholar
  49. Yang J, Zhou M, Yin P, Li M, Ou CQ, Gu S, Liu Q (2016) Mortality as a function of dust-haze in China: a multi-city time-series study. Lancet S19:31946–31948Google Scholar
  50. Yang S, Dong S, Qu X, Zhong X, Zhang Q (2017) Clinical significance of Wip1 over expression and its association with the p38MAPK/p53/p16 pathway in NSCLC. Mol Med Rep 15:719–723CrossRefGoogle Scholar
  51. Ye W, Huo T-T, Deng J-J, Dong F-Q, Liang B, Zhang Q-B (2015) Study on mutagenicity of four kinds of chrysotile asbestos. Journal of Toxicology 29:369–372 (in Chinese)Google Scholar
  52. Ye Q, Fu JF, Mao JH, Shen HQ, Chen XJ, Shao WX, Shang SQ, Wu YF (2016) Haze is an important medium for the spread of rotavirus. Environ Pollut 216:324–331CrossRefGoogle Scholar
  53. Zeng Y-L, Gan S-Y, Dong F-Q, Wang L-M, Deng J-J (2012) 4 major substitutes for chrysotile asbestos to organic acids characteristic and mechanism of in vitro cytotoxicity. Mod Prev Med 39:2938–2941 (in Chinese)Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Yali Zeng
    • 1
  • Yan Cui
    • 2
  • Ji Ma
    • 1
  • Tingting Huo
    • 3
  • Faqin Dong
    • 3
  • Qingbi Zhang
    • 2
  • Jianjun Deng
    • 1
  • Xu Zhang
    • 1
  • Jie Yang
    • 1
  • Yulin Wang
    • 1
  1. 1.Department of Clinical Laboratory404 Hospital of MianyangMianyangPeople’s Republic of China
  2. 2.School of Public HealthSouthwest Medical UniversityLuzhouPeople’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

Personalised recommendations