ABSTRACT
In India, a large number of tobacco chewers and masheri users are chronically exposed to tobacco genotoxicants. Detoxification processes involving cellular glutathione (GSH) and glutathione S-transferases (GST) determine the outcome of exposure to environmental mutagens including those present in tobacco. Hence, in this study, GSH levels, GST activity, GSTM1 genotype and cytogenetic damage were determined using lymphocytes from 114 smokeless tobacco habitues and controls. The study groups comprised of male tobacco chewers, female masheri users, and age- and sex-matched controls. Irrespective of the tobacco habit, GSH levels and GST activity were higher in females than in males. In both the groups of habitues, GSH levels were similar to those in controls, while a significant reduction in GST activity was observed in tobacco chewers only. The frequency of cytogenetic alterations was significantly elevated in both the groups of habitues with respect to controls. However, break-type aberrations were more frequent in tobacco chewers while gaps were commonly observed in masheri users. Differences in the nature of chromosomal alterations in the two groups of habitues appeared to be related to variation in total tobacco exposure and gender-related differences in the efficacy of the GSH/GST detoxification system.
Subject(s)
Chromosome Aberrations , Plants, Toxic , Tobacco, Smokeless , Case-Control Studies , Female , Genotype , Glutathione/metabolism , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Humans , MaleABSTRACT
Inhalation of tobacco dust is responsible for elevated genotoxicity and pulmonary ailments in workers engaged in processing tobacco for the manufacture of bidis, the Indian version of cigarettes. Tracheal tissue being the major site of interaction with tobacco dust, the effects of different concentrations of an aqueous extract of bidi tobacco (ATE) on the growth of a hamster tracheal epithelial cell line (HTE) were investigated. Colony forming efficiency assay revealed that ATE was cytotoxic only at the highest concentration of 5.0 mg/ml. In cultures treated with 1.25 mg/ml ATE, the cell doubling time and growth rate were similar to that of the controls, while a significant increase in cell doubling time (29.4+/-0.3 h vs 14.0+/-3.75 h, P<0.001) was observed at 2.5 mg/ml ATE concentration. Exposure of HTE cells to the non-toxic ATE concentration of 2.5 mg/ml was found to stimulate ornithine decarboxylase (ODC) activity, incorporation of [3H] methyl thymidine into DNA and increase in the S phase fraction was seen by flow cytometry. However, a 56% reduction in the growth rate of cultures treated with 2.5 mg/ml ATE was related to the prolongation of the traverse of cells through S phase. ATE-induced growth suppression was reversed when cultures were grown in ATE-free medium or upon repeated exposure to ATE. The findings suggest that increased tracheal cell proliferation induced by chronic inhalation of tobacco dust may contribute to the development of pulmonary disorders and possibly neoplasia in exposed individuals.
Subject(s)
Nicotiana/toxicity , Plants, Toxic , Trachea/drug effects , Trachea/pathology , Animals , Cell Cycle/drug effects , Cell Division/drug effects , Cell Line , Cricetinae , DNA/biosynthesis , Dust/adverse effects , Epithelial Cells/pathology , Flow Cytometry , Humans , Mesocricetus , Ornithine Decarboxylase/biosynthesis , Plant Extracts/toxicity , Scintillation Counting , Thymidine/chemistry , Nicotiana/chemistry , Trachea/metabolism , Tritium , Water/chemistryABSTRACT
Ambient and biological monitoring was undertaken among tobacco processors who are chronically exposed to tobacco particulates via nasopharyngeal and cutaneous routes. Ambient monitoring revealed that the inspirable dust concentration was 150-fold higher in the tobacco factory than in the control environment, and was associated with chronic bronchitis in workers. Increased systemic exposure to tobacco constituents was evident from the high levels of cotinine, thioethers, promutagens and direct acting mutagens in workers' urine. The mean glutathione level and glutathione S-transferase activity were significantly lower in the peripheral blood lymphocytes of workers; however, the frequency of the GSTM1 null allele was similar to that in controls. A significant increase in chromosomal damage was noted in target and non-target cells of tobacco processors. In view of the association between tobacco use and several non-communicable diseases, the findings of the present study indicate an urgent need to minimize tobacco exposure among the processors.
Subject(s)
Air Pollutants, Occupational/analysis , Environmental Monitoring , Nicotiana , Occupational Exposure/analysis , Plants, Toxic , Adolescent , Adult , Aged , Air Pollutants, Occupational/adverse effects , Blood Pressure , Chromosome Aberrations , Cotinine/analysis , Cotinine/urine , Dust/adverse effects , Dust/analysis , Female , Glutathione Transferase/blood , Glutathione Transferase/genetics , Humans , India , Middle Aged , Mutagenicity Tests , Pulse , Risk Factors , Saliva/chemistry , Nicotiana/adverse effectsABSTRACT
A human squamous cell carcinoma (SCC) cell line has been established from the surgical specimen of an untreated, upper aero-digestive tract tumour, diagnosed as a squamous carcinoma, grade III, of the pyriform fossa. The tumour tissue was grown as a xenograft in an athymic nude mouse and was designated as NT-8. Histological examination of the surgical specimen and the nude mouse tumour showed that the two were identical. NT-8 was subsequently passed by subcutaneous injections into nude mice. After the 6th passage in nude mouse, the tumour was cultured in vitro where it grew as an epithelial cell line, with a typical cobblestone appearance. This cell line was designated as NT-8e. Both the primary tumour as well as xenograft and the cells in culture have retained several common morphological and biochemical characteristics. Immunological markers for epithelial cells including epithelial membrane antigen and cytokeratins were seen in all three, confirming the epithelial lineage. Characterization of the NT-8e cell line including growth parameters, anchorage-independent growth and tumorigenicity in nude mice, chromosome counts and DNA content by flow cytometry have been carried out.
Subject(s)
Carcinoma, Squamous Cell/pathology , Cell Culture Techniques/methods , Pharyngeal Neoplasms/pathology , Animals , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/surgery , Cell Adhesion , Cell Division , Chromosome Mapping , DNA, Neoplasm/analysis , Humans , Keratins/analysis , Kinetics , Mice , Mice, Nude , Mucin-1/analysis , Pharyngeal Neoplasms/genetics , Pharyngeal Neoplasms/surgery , Proliferating Cell Nuclear Antigen/analysis , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
In India, workers engaged in processing of tobacco for the manufacture of bidis (the indigenous substitute for cigarettes) are chronically exposed to tobacco flakes and dust via the cutaneous and nasopharyngeal routes. Hence, workers in a tobacco processing factory were monitored for chromosomal aberrations (CA) using peripheral blood lymphocytes as the test system. Cytogenetic analysis revealed a significant increase in deletion fragments and chromatid gaps in the exposed group. The frequency of aberrant metaphases and the proportion of individuals with CA were significantly higher in workers than in controls, indicating that occupational exposure to tobacco imposes considerable genotoxicity among tobacco processors.