Coal tar pitch extract could induce chromosomal instability of human bronchial epithelial cells mediated by spindle checkpoint-related proteins

// Peng Zhang 1, 2, * , Zhitao Li 3, * , Na Wang 1, * , Guangcai Duan 1 , Wei Wang 1 , Yanming Feng 3 , Yong Zhao 1 , Lixia Wang 1 , Hansong Zhu 1 , Qiao Zhang 1 , Xiaozhuan Liu 3 , Weidong Wu 4 , Yongjun Wu 1 , Wu Yao 1 , Jing Wang 5 , Yiming Wu 1 and Feifei Feng 1 1 College of Public Health, Zhengzhou University, Zhengzhou, Henan, China 2 The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, Henan, China 3 Medical College, Henan University of Science and Technology, Luoyang, Henan, China 4 School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China 5 Department of Pulmonary, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China * These authors have contributed equally to this work Correspondence to: Feifei Feng, email: heartnessff@126.com Keywords: chromosomal instability, coal tar pitch extract, R band, multiplex fluorescence in situ hybridization (M-FLSH), spindle checkpoint Received: September 22, 2016     Accepted: March 21, 2017     Published: April 11, 2017 ABSTRACT Coal tar pitch (CTP) is a byproduct of coal tar distillation. The workers working with coal tar or in aluminum smelters, potrooms and carbon plants have the opportunities of exposing to coal tar pitch volatiles. Coal tar pitches from which polycyclic aromatic hydrocarbons (PAHs) originate have been shown to exhibit lung carcinogenicity in humans. Chromosomal instability (CIN) is a mechanism in carcinogenesis, however, whether CIN is involved in coal tar pitch-induced lung cancer remains elusive. In this present study, human bronchial epithelial cells (BEAS-2B) were first exposed to coal tar pitch extracts (CTPE) to induce a malignant transformation model. Then, the occurrence of severe chromosomal changes detected using G band, R band and multiplex fluorescence in situ hybridization (M-FISH) staining were examined. It was shown that more clones of transformed BEAS-2B cells at passage 30 following stimulation with CTPE were formed in the soft agar compared with the vehicle control. Moreover, the expression of the spindle checkpoint-related proteins, mitotic arrest defective 2 (Mad2), budding uninhibited in benzimidazole 1 (Bub1), and anaphase-promoting complex (APC), indicators of abnormal chromosomes and carcinogenesis, reduced in CTPE-treated BEAS-2B cells at Passage 30 compared with the vehicle control using real-time PCR and immunohistochemistry. In summary, exposure of BEAS-2B cells to CTPE may induce chromosomal instability through spindle checkpoint-related proteins.