The TSPO Ligands MGV-1 and 2-Cl-MGV-1 Differentially Inhibit the Cigarette Smoke-Induced Cytotoxicity to H1299 Lung Cancer Cells.

TSPO is involved in cigarette smoke (CS)-induced cellular toxicity, which may result in oral and pulmonary diseases and lung cancer. H1299 lung cancer cells were exposed directly to CS. The H1299 cells were pretreated with our TSPO ligands MGV-1 and 2-Cl-MGV-1 (Ki = 825 nM for both) at a concentration of 25 µM 24 h prior to CS exposure. Cell death and apoptotic markers were measured, in addition to TSPO expression levels, ATP synthase activity, generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), cAMP and LDH levels. Pretreatment with MGV-1 and 2-Cl-MGV-1 (25 µM), 24 h prior to CS exposure, differentially attenuated the CS-induced cellular insult as well as cell death in H1299 lung cancer cells. These protective effects included prevention of ATP synthase reversal, ROS generation, depolarization of the mitochondrial membrane and elevation in LDH. The preventive efficacy of 2-Cl-MGV-1 was superior to that achieved by MGV-1. Both ligands did not prevent the elevation in cAMP. These findings may indicate a mild protective effect of these TSPO ligands in CS-related pulmonary and keratinocyte cellular pathology.

18-kDa Translocator Protein Ligands Protect H9C2 Cardiomyocytes from Cigarette Smoke-induced Cell Death: In Vitro Study.

BACKGROUND: Cigarette smoke (CS) can induce cellular damage via alterations in 18 kDa translocator protein (TSPO)-related functions, leading to cardiovascular diseases. The current study focused on the possible protective effect of TSPO ligands against CS-induced damage to cardiac cells. MATERIALS AND METHODS: H9C2 Cardiomyocyte cell line of rat origin was pre-treated with TSPO ligands. Cell death, TSPO binding, and TSPO protein expression levels were assessed following 30-min CS exposure with/without TSPO ligands. RESULTS: CS exposure of H9C2 cells significantly incensed cell death (by 26%, p<0.001). Pre-treatment with TSPO ligands at two concentrations prevented cell death. Neither CS nor ligands affected TSPO protein expression in H9C2 cells. CS led to increased cell death and reduced TSPO binding. CONCLUSION: Reduced TSPO binding may have a role in CS-induced cell death, and TSPO ligand MGV-1 can prevent suppression of TSPO binding and corresponding cell death. These results may be relevant to treatment of cardiovascular diseases associated with CS.

Cigarette smoke, saliva, the translocator protein 18 kDa (TSPO), and oral cancer.

Oral squamous cell carcinoma (OSCC) incidence is induced primarily by cigarette smoke (CS). The 5-year survival rate for advanced OSCC stands at only 20%. Studies exploring underlying mechanisms of OSCC development have suggested free radicals such as reactive oxygen species generated by CS as contributing to OSCC, with effects enhanced by transition metal ions iron and copper contained in the saliva. Located on the outer mitochondrial membrane of various cell types, the 18-kDa translocator protein (TSPO) is up-regulated under pathological conditions such as cancer and inflammation. We focused on studying the interaction between TSPO, CS, salivary effects, and OSCC. Increased TSPO expression in OSCC tumors correlates significantly with reduced patient survival rate, indicating the possible role of TSPO in OSCC pathogenesis. We speculate that TSPO in OSCC is dysfunctional or mutated, rendering it ineffective in promoting apoptosis and blocking malignant transformation. Basal, precancer lower function of TSPO may diminish the TSPO capacity for pro-apoptotic and anti-cancer activity, resulting in development of OSCC. In order to overcome this, TSPO over-expression is induced, unfortunately with no benefit, as it is a malfunctioning TSPO, similar to cases where over-expression of a mutated form of the p53 gene in tumors is associated with carcinogenesis.

Non-primary salivary malignancies: A 22-year retrospective study.

PURPOSE: Most salivary gland malignancies are primary tumors, but in our medical center one of six is non-primary. The relative scarcity of such reports justifies studying them. SUBJECTS & METHODS: We studied patients' demographic and clinical parameters, salivary tumors/metastasis, diagnosis and treatment, and survival rates. RESULTS: Of all our salivary malignancy patients over the last 22 years, 15% (18/119) had non-primary malignant tumors, all located in the parotid glands. Of these, nine had skin cancer (SCC), 3 malignant solid tumors and 6 hematological systemic malignancies. Four had concomitant second malignancy. Mean age was 70.2 ± 13.8 years, 66.7% of the patients were males, 27.8% were smokers, none reported alcohol use. The most prevalent diagnostic tools used were CT (16 patients), FNA (13) and PET-CT (12). Eleven of 18 patients died from the disease despite receiving therapy: 6 SCC patients, 2 CLL patients and all 3 with solid tumors. All four lymphoma patients survived as did another three SCC patients. CONCLUSIONS: Chemotherapy and radiotherapy for systemic disease prolonged life rather than surgery. Patients with poor prognosis non-primary salivary tumors should be treated conservatively; surgery should be for those without widespread metastases or systemic disease. Sometimes a palliative patient may benefit from tumor debulking.

Effects of Cigarette Smoke on TSPO-related Mitochondrial Processes.

The 18 kDa translocator protein (TSPO) is an initiator of the mitochondrial apoptosis cascade. Cigarette smoke (CS) exposure provokes alterations in TSPO expression as well as upregulation of its related functions such as mitochondrial membrane potential (ΔψM) and reactive oxygen species generation, which are associated with cell death. In the current study, H1299 lung cancer cell line exposed to CS for various time periods (30 mins, 60 mins and 120 mins) and TSPO expression and cell death processes were studied. CS exposure for 30 mins resulted in a non-significant increase in TSPO expression by 24% (p > 0.05 vs. control). CS exposure for 60 mins and 120 mins resulted in a significant increase by 43% (p < 0.05 vs. control) and by 47% (p < 0.01 vs. control), respectively. Furthermore, TSPO-related mitochondrial functions were upregulated at the 120 mins time point following CS exposure. TSPO expression is upregulated by CS, suggesting that TSPO plays a role in cell death processes induced by CS exposure. Alterations in TSPO-related cell death processes suggest that TSPO may be involved in the tissue damage caused by CS.

Kaplan-Meier analysis of salivary gland tumors: prognosis and long-term survival.

PURPOSE: We evaluated the impact of various tumor related parameters on survival probability in a cohort of patients with malignant salivary tumors, using the Kaplan-Meier analysis. METHODS: We measured patients up to 15 years following therapy, looking at T N M stage, grade perineural invasion and extra-parenchymal spread. RESULTS: Of 101 patients diagnosed with various salivary malignant tumors in our medical center, 79 patients survived while 22 died with disease (DWD). The impact of distant metastasis (M+) was devastating (survival probability at 60 months and at 180 months dropped from 0.93 (M-) to 0.40 (M+) and from 0.67 to 0.40, respectively, p = 0.0001), the impact of perineural invasion was severe (at 180 months the probability of survival dropped from 0.75 to 0.21, p = 0.002). Higher stage tumor also decreased survival (from 0.82 to 0.53 at 180 months, p = 0.002) as did poor histological grade (from 0.85 to 0.48 at 180 months, p = 0.019). Neck metastasis (N+) impact was quite moderate (at 180 months the probability of survival dropped from 0.69 to 0.58, p = 0.044) while neither tumor size (T) nor extra-parenchymal spread significantly affected survival. CONCLUSIONS: Salivary tumor location and its potential to infiltrate nerves and blood vessels and to metastasize is the most telling parameter. Systemic therapy aimed at halting distant metastatic spread is the most effective therapeutic goal. Dissection of N0 neck metastasis is not necessarily a valuable treatment.

Mortality rates and prognostic factors in patients with malignant salivary tumors.

Malignancies of the salivary glands represent a multifarious disease. Evaluating the prognostic factors of these malignancies may help predict patient outcome and aid decision-making in choosing the most suitable therapy. We examined the role of various salivary tumorigenic, clinical and therapeutic features in a cohort of 101 patients diagnosed and treated for primary malignant salivary tumors. These include histo-pathological diagnosis, stage, grade and T, N, M values as well as the existence of perineural invasion and extra-parenchymal spread. We also identified the salivary gland involved, the sub-compartment specific location of the tumor and the therapy administered. All these were related to mortality. Of the 101 patients examined, 79 survived and 22 died due to the disease. Tumor staging, distant metastasis and perineural invasion were highly significant predictors of increased lethality. Histo-pathological grading was also a predictor but to a lesser degree. Neither neck metastasis nor tumor size or type had a significant impact on lethality. Performing neck dissections did not decrease lethality rate. Location of the tumor in the parotid gland and more so in its deep lobe adversely affected lethality; extra-parenchymal spread also had an adverse effect. Our results seem to indicate hematogenous rather than lymphogenous spread of metastasis from malignant salivary tumors. The highest therapeutic priority should be achieving full local control of the disease by safe removal of the primary salivary tumor, accompanied by regional control of perineural invasion and extra-parenchymal spread and appropriate systemic treatment aimed at eradicating distant metastasis.

Survival Probabilities Related to Histology, Grade and Stage in Patients With Salivary Gland Tumors.

BACKGROUND: The diversity of malignant salivary gland tumors challenges the study of survival rates. The current study evaluated patient survival rates using Kaplan-Meier analysis and examined the relative effects of histology, grade and stage on survival. MATERIALS AND METHODS: Using the Kaplan-Meier model, cancer-specific (CSS) and disease-free (DFS) survival probabilities were calculated as a function of time. RESULTS: Of 101 patients, 79 survived and 22 died of their disease. The probability of CSS was 0.83, 0.73 and 0.61 at 5, 10 and 15 years, respectively; corresponding probability of DFS was 0.69, 0.59 and 0.54, respectively. CONCLUSION: CSS and the DFS probabilities in patients with salivary malignancies were quite high at 5 years, although these rates dropped over the long-term; the lethal effect of the malignancy is often delayed and prolonged. Tumor histology, grade and stage are well established factors in predicting prognosis. Although the subgroups of patients with MECA and SCC were too small to allow adequate statistical analysis, clear tendencies for devastating effects of poor differentiation in SCC and higher grade in MECA were shown. That is, 2/4 patients with high-grade MECA died from their disease, while only 1/15 with low-intermediate grade MECA died from their disease. Similarly, 2/4 patients with poorly differentiated SCC died from their disease, while only 1/5 with well-to-moderately-differentiated SCC died from their disease. Factors such as molecular markers should be further studied in an effort to improve prognosis prediction.

Salivary malignancies- medical, demographic and diagnostic analysis.

We examined systemic medical and demographic characteristics of patients diagnosed with salivary malignant tumors in order to better understand the pathogenesis of the disease. Of 101 patients who received definitive treatment for malignant salivary gland tumors in our medical center, 22 died with disease (DwD) and were compared with the remaining 79 patients (Other). Mean ages were 66.7 years (median 68.0) in DwD group and 58.7 years (median 59.0) in the Others. The difference is significant (p = 0.037). Mucoepidermoid carcinoma was the diagnosis in 27.3% of DwDs and 27.8% of the others, Adenoidcystic carcinoma in 36.4% vs 21.5%, SCC and Acinic cell carcinoma were diagnosed in 18.3% vs 7.6% and 4.6% vs 7.6%, respectively. Alcohol consumption, concomitant malignancies, and chronic illnesses other than hypertension, were similar in the two groups, but hypertension (63.6%) in the DwD group was significantly higher than in the Other group (26.6%), (p = 0.0010). Smoking was also significantly different between the two groups: 50% of the DwD vs. 27.9% of the Others group smoked cigarettes. Similar distribution of the various malignant tumors in both groups emphasizes the relative importance of systemic factors such as smoking, aging and hypertension, in the salivary carcinogenesis process.

Transarterial Embolization in Maxillofacial Intractable Potentially Life-Threatening Hemorrhage.

PURPOSE: Although transarterial embolization (TAE) of vascular lesions with embolizing agents through angiographic catheters has been used for more than 45 years, reports of life-threatening maxillofacial bleeding are relatively rare and have not been updated. The authors review treatment modalities, present their experience of the past 21 years, and suggest a comprehensive algorithm and guidelines for the use of TAE in the treatment of intractable life-threatening maxillofacial hemorrhage. MATERIALS AND METHODS: This article describes 28 patients treated with TAE for severe bleeding that did not respond to conservative therapies. Of these, 13 had uncontrolled epistaxis, 9 were oncologic patients, 4 were postsurgical patients, and 2 were trauma patients. RESULTS: Details of patients' medical history, failed conservative therapy administered before TAE, imaging results, and blood vessels involved are presented, as are the TAE procedures and materials used, outcome, and complications. All these are discussed in relation to the available updated literature. All 9 oncologic patients (100%) had been treated with chemotherapy before the uncontrolled bleeding, and 7 also had radiotherapy administered to the maxillofacial region. Continuous anticoagulant therapy also seemed to predict such bleeding episodes. TAE resolved the bleeding in all 28 cases and rapidly in 90% of cases. Only in 3 oncologic cases did continued bleeding require 3 to 4 consecutive TAE sessions and combinations of embolizing agents. CONCLUSIONS: The reported high rate of success could be the result of careful techniques, appropriate preoperative imaging, highly professional personnel, and intraoperative and perioperative treatments.

Diagnostic and therapeutic modalities for 287 malignant and benign salivary tumors: A cohort study.

BACKGROUND: Salivary gland tumors (SGT's), 3-10% of head/neck tumors, exhibit a striking range of morphological diversity. This minimally symptomatic disease can be challenging to diagnose, and therapeutic policy is still controversial. METHODS: We compared benign and malignant cohorts according to diagnostic modality utilized and therapeutic modality administered over 20 years in a single medical center. RESULTS: Of 287 cases, 216 had benign tumors and 71 had malignant tumors. Treatment was surgery-based in 99% of cases, often accompanied by radiotherapy and/or chemotherapy. Rates of imaging and biopsy for diagnosis were significantly higher in malignant than benign tumors. Fine-needle aspiration (FNA) was used in 90.3% of benign tumors. Of 71 malignant tumors, 69 underwent surgery to fully remove the malignant tumor. Adjuvant therapy included 22 neck dissections (30%), 28 radiotherapy (39.4%), 12 chemotherapy (16.9%) and 10 combined radio-chemotherapy (14.1%). Partial parotidectomy, submandibular sialoadenectomy and local excision were used in 78.1%, 8.3% and 6.9% of benign cases. Total parotidectomy, sub-total maxillectomy and wide excision were used in 16.9%, 12.7% and 22.6% of malignant cases. DISCUSSION: Diagnostic and therapeutic modalities for treatment of salivary tumor at our hospital are presented and discussed with respect to others. A paradigm of therapy administered in our institute is presented.

Two populations of TSPO binding sites in oral cancer SCC-15 cells.

Oral cancer mortality and morbidity rates remain high. The main inducer of oral cancer is cigarette smoke (CS). Translocator protein 18kDa (TSPO) was shown to play a role in carcinogenesis. We characterized TSPO binding sites in human oral cancer cell line SCC-15 and examined effect of CS on TSPO binding. We exposed SCC-15 human squamous cells to cigarette smoke. [3H]PK 11195 binding results were assessed in cells confluent for one day. To characterize the number of population sites, a custom written Matlab program compared Pearson linear correlation coefficients between all points in the Scatchard plot. Using [3H]PK 11195 as a radio ligand, we found that TSPO binding sites are not uniform, but separated into two sub-populations, one with high affinity (respective Kd and Bmax values of 1.40±0.08nM and 1586±48 fmol/mg protein), another with lower affinity (respective Kd and Bmax values of 61±5nM and 26260±1050 fmol/mg protein). We demonstrate rapid decrease in TSPO binding to the high affinity site induced by exposure to CS; specifically, significant 36% decrease in binding after 30min CS exposure (p<0.05), and 69% decrease after 2h CS exposure (p<0.05). Association between TSPO and CS exposure may contribute to understanding the underlying mechanism of oral carcinogenesis.

Tumor Growth and Cell Proliferation Rate in Human Oral Cancer.

BACKGROUND AND AIMS: Oral squamous cell cancer (SCC) has a high rate of morbidity and an overall 5-year survival rate for patients of 50%, statistics that have not changed in the last half century. A better understanding of the biological nature of this aggressive disease is mandatory. The two most studied human oral cancer cell lines-SCC-15 and SCC-25-share some biological characteristics but differ in others and may serve as a platform for further oral SCC analysis. We compared their basic carcinogenic characteristics, cellular proliferation rate and tumor growth, and discussed results according to available data from the literature and our own previous studies. METHODS: We examined doubling time both in vitro and in vivo of the SCC-15 and SCC-25 cell lines. After seeding the exact same number of cells in a six-well dish we counted them daily. To confirm doubling time differences in cells, we progressed to an in vivo model in nude mice using male 9- to 10-week-old BALB/c-nu/nu mice. RESULTS: In both models (in vitro and in vivo) SCC-15 multiplied faster than SCC-25 cell line. In vivo the difference was more than double and in vitro this change was 24%. CONCLUSION: Both SCC-15 and SCC-25 cell lines are suitable for further exploration of the oral carcinogenesis process. Based on our currently presented results and on the available literature, it seems that SCC-15 has an increased potential for local tumor growth and cell proliferation, whereas SCC-25 has a higher potential for invasion and metastasis.

Benign and Malignant Salivary Gland Tumors - Clinical and Demographic Characteristics.

AIM: To examine the demographic, ethnic, and clinical characteristics of salivary benign and malignant tumors for better etiological understanding. PATIENTS AND METHODS: We examined medical records of 287 primary salivary gland tumor patients. RESULTS: Overall, 216 tumors were benign and 71 malignant. The mean age at diagnosis was 56.4 years for those with malignant tumors and 48.5 years for those with benign, a highly significant difference (p=0.001). Females had 45% of malignant tumors and 59% of benign, a significant difference (p=0.037). Ethnic origin, alcohol consumption and cigarette smoking rates were not significantly different (p>0.05) between groups. A total of 87% of benign and 55% of malignant tumors were in the parotid glands, a highly significant predilection (p<0.0001), sublocated mostly in the superfacial lobe; 36.6% of malignant tumors and 4.7% of benign (p<0.0001) were in the minor salivary glands, mostly in the hard palate. CONCLUSION: Baseline clinical, demographic and locational aspects of benign and malignant tumors are substantiated.

Cigarette smoke effects on TSPO and VDAC expression in a cellular lung cancer model.

As redox iron and copper ions are found in lung pleural fluid and parenchyma, we aimed to examine the effect of cigarette smoke (CS) alone and the combined effects of CS and redox metals, iron and copper ions, containing medium (saliva), on epithelial H1299 lung cancer cells. We also examined the expression levels of the anticarcinogenic and proapoptotic 18 kDa translocator protein (TSPO) and its closely associated protein voltage-dependent anion channel (VDAC). H1299 cells were subjected to western blot analysis using anti-TSPO and anti-VDAC antibodies. With the former, the 18 kDa band appeared as expected and a 72 kDa band also appeared. It may be assumed that in H1299 lung cancer cells, an additional form of TSPO protein appears as a four-unit tetrameric complex, which is affected by CS exposure. A significant decrease in the expression level of the 72 kDa protein occurred following only 60 min of CS exposure, whereas VDAC protein levels were increased following only 30 min of CS exposure. These results, together with our previous related studies, suggest a comprehensive two-arm novel paradigm for lung cancer induced by CS, and mediated by an altered TSPO protein, possibly resulting from both the 72 kDa TSPO degradation and redox metal ion-induced enhancement of free radical attack. We suggest that both of the most important proapoptotic and anticancer proteins, p53 and TSPO, are damaged by CS, paving the way for lung cancer initiation and progression.

The Effect of Cigarette Smoke on the Translocator Protein (TSPO) in Cultured Lung Cancer Cells.

Lung cancer is prevalent in cigarette smokers. The mitochondrial membrane translocator protein (TSPO), is thought to protect cells from free radical damage. We examined the effect of cigarette smoke (CS) (containing free radicals) alone and in the presence of saliva (containing redox active free iron), on survival of H1299 lung cancer cells and on their mitochondrial characteristics, and whether TSPO binding was influenced by CS and by saliva. We exposed H1299 cells to CS in the presence/absence of saliva and also characterized TSPO binding in the cells using [3H]PK 11195 as a radioligand. CS induced a significant drop in mitochondrial potential (ΔΨm), while addition of saliva did not lead to further loss of ΔΨm (42.5% vs. 39.85%). Scatchard analysis of the saturation curve of [3H]PK 11195 binding (0.2-6 nM final concentration) yielded a straight-line plot (R = 0.9). Average Bmax value was 3274 ± 787 fmol/mg of protein, and average Kd value was 9.2 ± 1.3 nM. Benzodiazepine diazepam partially prevented decrease in cell survival following exposure to CS and redox active iron containing media (saliva) while benzodiazepine clonazepam did not, indicating that this effect is TSPO-specific. Exposure of cells to CS resulted in alternation of biomolecules expressed by CLs peroxidation, reduction of TSPO binding, and depletion of the mitochondrial potential. This irreversible damage was enhanced in the presence of saliva. All these modulations may result in cellular death increase following CS exposure, enhanced in the presence of saliva.

Bypassing the emergency room to reduce door-to-balloon time and improve outcomes of ST elevation myocardial infarction patients: analysis of data from 2004-2010 ACSIS registry.

OBJECTIVES: Our objective was to assess whether bypassing the emergency room (ER) is associated with meaningful reduction in Major Adverse Cardiac and Cerebrovascular Event (MACCE) or mortality in a large cohort of ST Elevation Myocardial Infarction (STEMI) patients. BACKGROUND: Prior studies suggest that bypassing the emergency room reduces door-to-balloon time (DBT). However, it is not clear whether this translates into reduced mortality. METHODS: We analyzed data of 1,552 consecutive patients with STEMI treated by primary percutaneous coronary intervention (PCI) and enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) registry. Thirty percent of patients (n = 459) arrived directly to the Intensive Cardiac Care Unit or catheterization laboratory and 70% (n = 1093) were assessed first in the ER. Our primary end points were DBT, 30-day MACCE, and 30-day and 1-year mortality. Our secondary end points were pre-discharge ejection fraction less than 40%, in-hospital pulmonary edema, in-hospital cardiogenic shock, ST resolution, and duration of hospitalization. RESULTS: Bypassing the ER was associated with signficantly shorter DBT (59 vs. 97 minutes, P = 0.001). There was no difference in 30-day MACCE and 30-day or 1-year mortality between the 2 study groups. The findings were consistent in multiple subgroups, including women, anterior STEMI, off hours PCI, and patients with pain-to-door (PDT) time of less than 120 minutes. CONCLUSION: Bypassing the ER is associated with significant shortening of DBT. This reduction, however, is not associated with any change in 30-day MACCE and 30-day or 1-year mortality.

Carbonyl levels and survival rates in oral cancer cells exposed to cigarette smoke.

BACKGROUND: Cigarette smoke (CS) is the main inducer of oral cancer, increasing prevalence 4-7 times. MATERIALS AND METHODS: We examined SCC-25 and SCC-15 suitability for studying CS effects on oral cancer cells, measuring carbonyl levels for free radical-mediated CS effect on survival and time/CS dependence. RESULTS: Protein oxidation increased significantly during CS exposure. At all time points, carbonyl levels increased six-fold (p<0.001) in both cell lines. Cell viability decrease was time-dependent. Longer CS exposure led to higher cell mortality. At 120 min, SCC-25 cell survival reduction was 43.7%, (p<0.01). Propidium iodide (PI) assay results matched the Trypan blue assay showing a time-dependent cell viability decrease following CS exposure. At 120 min, cell survival reduction was 37% (p<0.05). CONCLUSION: Cell death is mediated by CS free radicals with pathological process occurring first. Oral cancer cell models SCC-25 and SCC-15 are suitable for studying CS-induced free radical-related damage, potentially leading to the pathogenesis of oral cancer.

Cigarette smoke-induced effects on the cell cycle in oral cancer cells: reduction of G2/M fraction.

BACKGROUND: Cigarette smoke (CS) is the main inducer of oral cancer, increasing its prevalence by 4-7 times. MATERIALS AND METHODS: We examined the suitability of cell models SCC-25 and SCC-15 for studying effects of CS on oral cancer cells and whether CS significantly affects the cell cycle using fluorescence-activated cell sorting assays. RESULTS: There was significant change in the fraction of SCC-15 cells in pre-G1 state following CS exposure. At 60 and 90 min, increase in the pre-G1 cell fraction was 118% (p<0.05) and 135% (p<0.01) respectively. The G2/M cell fraction was significantly lower following CS exposure. At 90 and 120 min following CS exposure, the G2/M fraction levels had declined by 44% (p<0.05) and 34% (p<0.01) respectively. Results for SCC-25 cells were similar. At 90 and 120 min following CS exposure, the pre-G1 fraction of the cells increased by 230% and 550%, respectively (p<0.01). At 120 min of CS exposure, the fraction of G2/M cells was lower by 47% (p<0.05) compared to controls. CONCLUSION: CS profoundly affects the cell-cycle distribution in both SCC-15 and SCC-25 oral cancer cellular models. Such effects have been associated with DNA damage and carcinogenesis. Both models are useful for studying oral cancer pathogenesis.