Chemical composition, cytotoxicity and mutagenicity of smoke from US commercial and reference cigarettes smoked under two sets of machine smoking conditions
“…Thus, we treated pre-malignant MCF10AT cells with B[a]P and CSC in parallel experiments and compared our results. The referenced cigarettes, 1R4F, have a tar or CSC content of about 10 mg/cigarette, which contains about 6.94 ng of B[a]P (Stabbert et al, 2003;Roemer et al, 2004). Clearly, the concentrations of CSC (0-50 mg/ml) employed in our studies were very low in comparison to the amount present in a cigarette.…”
Section: Discussionmentioning
confidence: 77%
“…However, how much of the CSC was taken up by the cells is not known. Based on urinary metabolites, it has been estimated that the uptake of nicotine and B[a]P amounts to 1.1 mg and 0.01 mg/ cigarette, respectively (Roemer et al, 2004). In our experiments based upon IC 50 concentration, 0-12.5 mg/ml of B[a]P was used, which was much higher than the amount taken up by the cells as estimated by Roemer et al (2004).…”
Section: Discussionmentioning
confidence: 87%
“…Based on urinary metabolites, it has been estimated that the uptake of nicotine and B[a]P amounts to 1.1 mg and 0.01 mg/ cigarette, respectively (Roemer et al, 2004). In our experiments based upon IC 50 concentration, 0-12.5 mg/ml of B[a]P was used, which was much higher than the amount taken up by the cells as estimated by Roemer et al (2004). However, it is important to consider that only a small portion of the B[a]P present in the culture medium comes in contact with cells, and their uptake is further influenced by cellular factors.…”
Our previous studies have shown that treatment with cigarette smoke condensate (CSC) transforms normal breast epithelial cell line, MCF-10A. In the present study, the mechanism of CSC-induced transformation of breast epithelial cells was examined. We first determined whether benzo[a]pyrene (B[a]P)-and CSC-induced levels of APC are capable of inhibiting long-patch base excision repair (LP-BER) since our earlier studies had shown that an interaction of APC with DNA polymerase b (pol-b) blocks strand-displacement synthesis. With the use of a novel in vivo LP-BER assay, it was demonstrated that increased and decreased APC levels in different breast cancer cell lines were associated with a decrease or increase in LP-BER activity, respectively. The effect of APC on LP-BER in malignant and pre-malignant breast epithelial cell lines was produced by either overexpression or knockdown of APC. Furthermore, it was shown that the decreased LP-BER in B[a]P-or CSC-treated premalignant breast epithelial cells is associated with an increased level of APC and decreased cell growth. Our results suggest that the decreased growth allows cells to repair the damaged DNA before mitosis, and failure to repair damaged DNA has the potential to transform premalignant breast epithelial cells.
“…Thus, we treated pre-malignant MCF10AT cells with B[a]P and CSC in parallel experiments and compared our results. The referenced cigarettes, 1R4F, have a tar or CSC content of about 10 mg/cigarette, which contains about 6.94 ng of B[a]P (Stabbert et al, 2003;Roemer et al, 2004). Clearly, the concentrations of CSC (0-50 mg/ml) employed in our studies were very low in comparison to the amount present in a cigarette.…”
Section: Discussionmentioning
confidence: 77%
“…However, how much of the CSC was taken up by the cells is not known. Based on urinary metabolites, it has been estimated that the uptake of nicotine and B[a]P amounts to 1.1 mg and 0.01 mg/ cigarette, respectively (Roemer et al, 2004). In our experiments based upon IC 50 concentration, 0-12.5 mg/ml of B[a]P was used, which was much higher than the amount taken up by the cells as estimated by Roemer et al (2004).…”
Section: Discussionmentioning
confidence: 87%
“…Based on urinary metabolites, it has been estimated that the uptake of nicotine and B[a]P amounts to 1.1 mg and 0.01 mg/ cigarette, respectively (Roemer et al, 2004). In our experiments based upon IC 50 concentration, 0-12.5 mg/ml of B[a]P was used, which was much higher than the amount taken up by the cells as estimated by Roemer et al (2004). However, it is important to consider that only a small portion of the B[a]P present in the culture medium comes in contact with cells, and their uptake is further influenced by cellular factors.…”
Our previous studies have shown that treatment with cigarette smoke condensate (CSC) transforms normal breast epithelial cell line, MCF-10A. In the present study, the mechanism of CSC-induced transformation of breast epithelial cells was examined. We first determined whether benzo[a]pyrene (B[a]P)-and CSC-induced levels of APC are capable of inhibiting long-patch base excision repair (LP-BER) since our earlier studies had shown that an interaction of APC with DNA polymerase b (pol-b) blocks strand-displacement synthesis. With the use of a novel in vivo LP-BER assay, it was demonstrated that increased and decreased APC levels in different breast cancer cell lines were associated with a decrease or increase in LP-BER activity, respectively. The effect of APC on LP-BER in malignant and pre-malignant breast epithelial cell lines was produced by either overexpression or knockdown of APC. Furthermore, it was shown that the decreased LP-BER in B[a]P-or CSC-treated premalignant breast epithelial cells is associated with an increased level of APC and decreased cell growth. Our results suggest that the decreased growth allows cells to repair the damaged DNA before mitosis, and failure to repair damaged DNA has the potential to transform premalignant breast epithelial cells.
“…Such a high lung cancer risk is due to the physical-chemical characteristics of the mainstream cigarette smoke (MSS). In fact, the cigarette-generated particles contain more than 3500 semi-volatile and non-volatile compounds, some of them classified as carcinogenic such as hydrocarbons (PAHs; [24][25][26][27]), dioxins and furans [28], heavy metals [25,[29][30][31][32][33][34], and tobacco-specific nitrosamines [25,31,[35][36][37]. Moreover, in fresh unaged tobacco cigarette mainstream smoke particle concentrations of about 4 × 10 9 part cm −3 were measured, with an arithmetic mean diameter of about 0.2 µm [38][39][40][41].…”
Cigarette smoke is the main cause of lung cancer events. Mainstream cigarette smoke (MSS) is a direct concern for smokers, but also the secondhand smoke (SHS) contributes to the smoker exposure. In addition, smoker exposure is affected by the "free-smoke" particle exposure (B), related to the micro-environments where smokers spend time. The aim of this paper is to evaluate the daily alveolar and tracheobronchial deposited fractions of airborne particles for smokers as the sum of these three contributions: MSS, SHS, and B. Measurements of particle surface area distributions in the MSS were performed through a Scanning Mobility Particle Sizer, an Aerodynamic Particle Sizer, and a Thermo-dilution system on five types of conventional cigarettes. A Monte Carlo method was then applied to evaluate the most probable value of dose received during the inhalation of MSS by smokers. Measurements of particle concentrations in SHS and at the "free-smoke" particle background (B) were performed through 24-h monitoring at a personal scale of adult smoker through hand-held devices. This paper found that the total daily deposited dose for typical smokers was 1.03 × 10 5 mm 2 ·day −1 . The main contribution of such a huge daily dose was addressable to the MSS (98%) while SHS contributed 1.1%, increasing up to 2% for people smoking only while traveling in a car.
“…Levels of acrolein in cigarette smoke are 18-98 g per cigarette (8). Acrolein is an intense irritant and displays a range of toxic effects, including cilia toxicity (15,16).…”
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