Abstract
The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(b)fluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). After a 24-hour exposure, EGFR was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells. After only a 24-hour exposure, cells exhibited atypical nuclear and cytoplasmic features. After a 48-hour exposure, EGFR staining was localized to the nucleus, BCL-2 was slightly decreased in intensity, BIRC5 was localized to the cytoplasm, and TP53 staining was increased in small and large cells. BCL2L1 was expressed in both the cytoplasm and nuclei of cells at 24- and 48-hour exposures. We illustrate that short-termexposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens alters the expression of key proliferation regulatory genes, EGFR, BCL-2, BCL2L1, BIRC5, TP53, and MKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions.
Highlights
Cigarette smoking is a major cause of lung cancer. 90% of male and 75–80% of female lung cancer deaths in the USA are smoking related [1]
After a 24-hour exposure, Epidermal growth factor receptor (EGFR) was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells
After a 48-hour exposure, EGFR staining was localized to the nucleus, BCL-2 was slightly decreased in intensity, BIRC5 was localized to the cytoplasm, and TP53 staining was increased in small and large cells
Summary
Cigarette smoking is a major cause of lung cancer. 90% of male and 75–80% of female lung cancer deaths in the USA are smoking related [1]. Cigarette smoking is a major cause of lung cancer. 90% of male and 75–80% of female lung cancer deaths in the USA are smoking related [1]. As defined by the International Agency for Research on Cancer (IARC), each cigarette contains a mixture of more than 60 known carcinogens [2]. At least twenty of these carcinogens have been linked to tumors [1]. Bronchial epithelium undergoes a stepwise preneoplastic process encompassing various morphological and molecular changes before overt development of lung cancer [3]. There is no immunohistochemical or morphological marker, available for metaplasia, dysplasia, or carcinoma insitu, which reliably predicts the biological behavior of preneoplastic lesions
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