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

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.