Long‐term exposure to extremely low‐dose of nicotine and 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) induce non‐malignant breast epithelial cell transformation through activation of the a9‐nicotinic acetylcholine receptor‐mediated signaling pathway

Autor: Yun-Ru Liu, Chi-Cheng Huang, Li-Ching Chen, Tzu-chun Cheng, Hui Wen Chang, Wendy W. Hwang-Verslues, Hang‐Lung Chang, Chih-Hsiung Wu, Abdul-Fattah Salah Fararjeh, Yuan Soon Ho, Shih Hsin Tu, Hwa-Chain Robert Wang
Rok vydání: 2018
Předmět:
Nicotine
Nitrosamines
Time Factors
Health
Toxicology and Mutagenesis
Breast Neoplasms
Receptors
Nicotinic
010501 environmental sciences
Management
Monitoring
Policy and Law
Toxicology
medicine.disease_cause
01 natural sciences
Tobacco smoke
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Humans
Tobacco-specific nitrosamines
Mammary Glands
Human
Toxicity Tests
Chronic
Cells
Cultured
Cell Proliferation
0105 earth and related environmental sciences
Dose-Response Relationship
Drug
biology
Cell growth
CD44
Cancer
Epithelial Cells
General Medicine
medicine.disease
Acetylcholine
Cell Transformation
Neoplastic
chemistry
Nitrosamine
030220 oncology & carcinogenesis
Carcinogens
biology.protein
Cancer research
Female
Carcinogenesis
Signal Transduction
medicine.drug
Zdroj: Environmental Toxicology. 34:73-82
ISSN: 1522-7278
1520-4081
DOI: 10.1002/tox.22659
Popis: Breast cancer (BC) is the most common cancer affecting women worldwide and has been associated with active tobacco smoking. Low levels of nicotine (Nic) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have been detected in cases of second-hand smoke (SHS). However, the correlation between SHS and BC risk remains controversial. In this study, we investigated whether the physiological SHS achievable dose of Nic and tobacco specific nitrosamine, NNK act together to induce breast carcinogenesis using an in vitro breast cell carcinogenesis model. Immortalized non-tumorigenic breast epithelial cell line, HBL-100 used for a time-course assay, was exposed to very low levels of either Nic or NNK, or both. The time-course assay consisted of 23 cycles of nitrosamines treatment. In each cycle, HBL-100 cells were exposed to 1pM of Nic and/or 100 femtM of NNK for 48 hours. Cells were passaged every 3 days and harvested after 10, 15, and 23 cycles. Our results demonstrated that the tumorigenicity of HBL-100, defined by soft agar colony forming, proliferation, migration and invasion abilities, was enhanced by co-exposure to physiologically SHS achievable doses of Nic and NNK. In addition, α9-nAChR signaling activation, which plays an important role in cellular proliferation and cell survival, was also observed. Importantly, an increase in stemness properties including the prevalence of CD44+/CD24- cells, increase Nanog expression and mammosphere-forming ability were also observed. Our results indicate that chronic and long term exposure to environmental tobacco smoke, may induce breast cell carcinogenesis even at extremely low doses.
Databáze: OpenAIRE
Externí odkaz: