Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation.

Pancreatic cancer is the fourth leading cause of cancer-associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers.

Inorganic arsenic inhibits the nucleotide excision repair pathway and reduces the expression of XPC.

Chronic exposure to arsenic, most often through contaminated drinking water, has been linked to several types of cancer in humans, including skin and lung cancer. However, the mechanisms underlying its role in causing cancer are not well understood. There is evidence that exposure to arsenic can enhance the carcinogenicity of UV light in inducing skin cancers and may enhance the carcinogenicity of tobacco smoke in inducing lung cancers.

Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway.

Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER) pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke.

Bhas 42 cell transformation activity of cigarette smoke condensate is modulated by selenium and arsenic.

Cigarette smoking remains a major health risk worldwide. Development of newer tobacco products requires the use of quantitative toxicological assays. Recently, v-Ha-ras transfected BALB/c3T3 (Bhas 42) cell transformation assay was established that simulates the two-stage animal tumorigenesis model and measures tumor initiating and promoting activities of chemicals.

Impact of apigenin and kaempferol on human head and neck squamous cell carcinoma.

Objective: Apigenin and kaempferol are plant flavonoids with reported chemopreventive activities. This study aimed to determine the effect of apigenin and kaempferol on cell viability in cultured cells derived from the pharynx (FaDu cell line), an oral cavity carcinoma (PCI-13 cell line), and a metastatic lymph node (PCI-15B cell line) and in explanted FaDu cells.

Study Design: The in vitro viability of FaDu, PCI-13, and PCI-15B cells treated with apigenin and kaempferol was determined.

Adenomatous polyposis coli-mediated accumulation of abasic DNA lesions lead to cigarette smoke condensate-induced neoplastic transformation of normal breast epithelial cells.

Adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation, and apoptosis. Recently, we found a new role of APC in base excision repair (BER) and showed that it interacts with DNA polymerase β and 5'-flap endonuclease 1 and interferes in BER. Previously, we have also reported that cigarette smoke condensate (CSC) increases expression of APC and enhances the growth of normal human breast epithelial (MCF10A) cells in vitro.

Dietary selenium fails to influence cigarette smoke-induced lung tumorigenesis in A/J mice.

The goal of the study was to determine if dietary selenium inhibited the induction of lung tumorigenesis by cigarette smoke in A/J mice. Purified diets containing 0.15, 0.

Oxidative DNA adducts detected in vitro from redox activity of cigarette smoke constituents.

Cigarette smoke contains a variety of carcinogens, cocarcinogens, mutagens, and tumor promoters. In addition to polycyclic aromatic carcinogens and tobacco-specific nitrosamines, cigarette smoke also contains an abundance of catechols, aldehydes, and other constituents, which are DNA damaging directly or indirectly; therefore, they can also contribute to cigarette smoke-mediated carcinogenicity. In this study, we investigated the potential of cigarette smoke constituents to induce oxidative damage to DNA through their capacity to redox cycle.

Atherogenic and pulmonary responses of ApoE- and LDL receptor-deficient mice to sidestream cigarette smoke.

Plasma lipoproteins play important roles in the development and progression of atherosclerosis. Two widely used mouse models of experimental atherosclerosis, apolipoprotein E-deficient (ApoE -/-) and LDL receptor-deficient (LDLr -/-) mice, have major differences in lipoprotein characteristics. These include differences in lipoprotein cholesterol distribution, lipoprotein compositions, apoliporoteins distribution, and susceptibility to oxidation.

Cigarette smoke condensate-induced oxidative DNA damage and its removal in human cervical cancer cells.

Exposure to cigarette smoke is well documented to increase oxidative stress and could account for higher risk of cervical cancer in smokers. Cervical pre-cancerous lesions that are initiated by human papillomavirus (HPV) infection generally regress in the absence of known risk factors such as smoking. 8-oxodeoxyguanosine (8-oxodG) is a highly mutagenic oxidative DNA lesion that is formed by the oxidation of deoxyguanosine.

Decreased cytochrome c oxidase IV expression reduces steroidogenesis.

Steroidogenic acute regulatory protein facilitates the translocation of cholesterol to the inner mitochondrial membrane, thereby initiating steroidogenesis. At the inner mitochondrial membrane, cytochrome P450 side-chain cleavage enzyme converts cholesterol to pregnenolone, an oxidative process requiring electrons from NADPH. Pregnenolone then serves as the substrate for the formation of progesterone or dehydroepiandrosterone by downstream enzymes.

In utero tobacco smoke exposure alters pulmonary responses of newborn rats to ozone.

Prenatal tobacco smoke (TS) exposure has been implicated in various adverse health outcomes in the offspring, including poor development of lung and immune system, which in turn can alter the response of neonates to environmental challenges. This study was performed to determine whether in utero exposure to TS influences the pulmonary response of newborn rat pups to ozone (O₃). Timed pregnant Sprague-Dawley (SD) rats were exposed to TS or air for 3 h/d from gestation d 7 through 21.

Effects of cigarette smoke on the activation of oxidative stress-related transcription factors in female A/J mouse lung.

Cigarette smoke contains a high concentration of free radicals and induces oxidative stress in the lung and other tissues. Several transcription factors are known to be activated by oxidative stress, including nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and hypoxia-inducible factor (HIF). Studies were therefore undertaken to examine whether cigarette smoke could activate these transcription factors, as well as other transcription factors that may be important in lung carcinogenesis.

Early changes in gene expression induced by tobacco smoke: Evidence for the importance of estrogen within lung tissue.

Lung cancer is the leading cause of cancer deaths in the United States, surpassing breast cancer as the primary cause of cancer-related mortality in women. The goal of the present study was to identify early molecular changes in the lung induced by exposure to tobacco smoke and thus identify potential targets for chemoprevention. Female A/J mice were exposed to either tobacco smoke or HEPA-filtered air via a whole-body exposure chamber (6 h/d, 5 d/wk for 3, 8, and 20 weeks).

Enhanced platelet reactivity and thrombosis in Apoe-/- mice exposed to cigarette smoke is attenuated by P2Y12 antagonism.

Introduction: Smoking increases the risk of acute arterial thrombosis, including myocardial infarction, likely due to multi-factorial effects on the vasculature. Heightened platelet reactivity may be among the adverse effects of smoke exposure.

Methods: To examine the effects of smoke exposure on platelet function in an atherosclerotic environment, Apoe-deficient female mice, maintained on a Western diet, were exposed (4 hrs/d, 5 d/wk) to sidestream cigarette smoke in a whole-body exposure chamber for 12 weeks.

Dietary coenzyme Q10 does not protect against cigarette smoke-augmented atherosclerosis in apoE-deficient mice.

Dietary coenzyme Q10 reduces spontaneous atherosclerosis in the apoE-deficient mouse model of experimental atherosclerosis. We have shown previously that exposure to sidestream cigarette smoke (SSCS) enhances atherosclerotic lesion formation in apoE-deficient mice. The aim of the present study was to determine if CoQ10 protected against SSCS-mediated atherosclerosis.

Acute pulmonary response of mice to multi-wall carbon nanotubes.

Widespread use of carbon nanotubes is predicted for future and concerns have been raised about their potential health effects. The present study determined the pulmonary response of mice to multi-wall carbon nanotubes (MWCNTs). The MWCNT suspension in sterile phosphate-buffered saline (PBS) was introduced into mice lungs by oropharyngeal aspiration.

Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells.

Human papillomavirus (HPV) is the causative factor in the development and progression of cervical cancers in >97% of the cases, although insufficient. Epidemiological studies suggest an elevated risk of cervical cancer for cigarette smokers; therefore, we examined cigarette smoke-induced DNA damage and repair in HPV16-transformed human ectocervical cells (ECT1/E6 E7). Cells were treated with cigarette smoke condensate (CSC) for 72 h to assess the formation of single- and double-strand DNA breaks, measured by alkaline and neutral single cell gel electrophoresis assays, respectively.

Effect of dietary selenium and cigarette smoke on pulmonary cell proliferation in mice.

The objective of this study was to determine if dietary selenium could inhibit pulmonary cell proliferation in control and cigarette smoke-exposed female A/J mice. Selenium in the form of sodium selenite was supplemented to purified diets similar to the AIN-93M diet to yield 0.15, 0.

Naphthoquinones and bioactive compounds from tobacco as modulators of neuronal nitric oxide synthase activity.

Studies were conducted with extracts of several varieties of tobacco in search of neuronal nitric oxide synthase (nNOS) inhibitors which may be of value in the treatment of stroke. Current therapies do not directly exploit modulation of nNOS activity due to poor selectivity of the currently available nNOS inhibitors. The properties of a potentially novel nNOS inhibitor(s) derived from tobacco extracts, and the concentration-dependent, modulatory effects of the tobacco-derived naphthoquinone compound, 2,3,6-trimethyl-1,4-naphthoquinone (TMN), on nNOS activity were investigated, using 2-methyl-1,4-naphthoquinone (menadione) as a control.

Cigarette smoke, inflammation, and lung injury: a mechanistic perspective.

Inflammation is a common feature in the pathogenesis of cigarette smoke-associated diseases. The recruitment of inflammatory cells into the lung following cigarette smoke exposure presents a risk of tissue damage through the release of toxic mediators, including proteolytic enzymes and reactive oxygen species. This review represents a toxicological approach to investigation of cigarette smoke-induced lung injury, with a focus on laboratory studies and an emphasis on inflammatory mechanisms.

Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer.

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis.

C/EBPbeta-mediated transcriptional regulation of bcl-xl gene expression in human breast epithelial cells in response to cigarette smoke condensate.

In earlier studies, we have shown that cigarette smoke condensate (CSC), a surrogate for cigarette smoke, is capable of transforming the spontaneously immortalized human breast epithelial cell line, MCF10A. These transformed cells displayed upregulation of the anti-apoptotic gene, bcl-xl. Upregulation of this gene may impede the apoptotic pathway and allow the accumulation of DNA damage that can lead to cell transformation and carcinogenesis.

Acute pulmonary effects of combined exposure to carbon nanotubes and ozone in mice.

Ozone (O3) is a well-investigated gaseous air pollutant known to produce acute and chronic toxicity in the respiratory system. Whether prior exposure to nanoparticles influences the toxicity of O3 has not been well investigated. To determine if there are toxicological interactions between particulate and gas exposures, we examined acute pulmonary effects of a 3-h ozone exposure (0.

Molecular mechanism of reduction in pregnenolone synthesis by cigarette smoke.

Steroidogenic acute regulatory protein (StAR) facilitates the movement of cholesterol from the outer to inner mitochondrial membrane for the synthesis of pregnenolone. Here, we investigated the molecular mechanism of the reduction of pregnenolone synthesis by cigarette smoke condensate (CSC). Pre-exposure or post-exposure of cells with CSC led to reduced pregnenolone synthesis, in a fashion similar to its effect on isolated mitochondria.