In-vitro anticancer activity against Caco-2 cell line of colloidal nano silver synthesized using aqueous extract of Eucalyptus Camaldulensis leaves.

In the current study, we investigated the anticancer potential against human colon cells (Caco-2) of colloidal nanosilver (CN-Ag) produced in Syria using bioactive compounds in the aqueous extract of Eucalyptus camaldulensis leaves (AEECL). The formation of AgNPs was confirmed by UV-visible spectroscopy analysis with surface plasmon peak at 449 nm and their average size was found to be 12, 10, 23 nm by SEM, DLS and NTA respectively. This small size has confirmed the effective role of AEECL as capping agent. Further morphological characterization was done by EDS showed the presence of metallic silver. Zeta potential value (-23 mV) indicated the repulsion among the particles and stability of the formulation nanosilver. The anticancer effect of synthesized CN-Ag against Caco-2 has been tested. The cytotoxicity assay showed a dose-dependent and a time-dependent effect of CN-Ag. The high cytotoxicity of CN-Ag at low concentration (5µ/mL) open new prospects for the development of novel therapeutic approaches against human colon cancer Caco-2.

Randomized clinical trial of platysma muscle suture versus no suture for wound closure after thyroid surgery.

BACKGROUND: Suturing the platysma muscle during wound closure after thyroid surgery is frequently described in the literature. There is no prospective evidence to support its use or benefit. The aim of this study was to evaluate how a platysma muscle suture influences initial postoperative pain following thyroid surgery. METHODS: Patients were assigned randomly to receive a platysma suture or no platysma suture in this prospective, patient-blinded trial. The duration of follow-up was 6 months. The primary endpoint was wound-specific pain 24 h after thyroid resection. Secondary endpoints were intraoperative and perioperative analgesia requirement, postoperative pain and complications until postoperative day 14, and Patient and Observer Scar Assessment Score (POSAS) 6 months after surgery. RESULTS: Forty-one patients were randomized to each group. Visual analogue scale scores for wound-specific pain were lower in patients without a platysma suture 24 h after surgery (mean(s.d.) 3·15(1·46) versus 2·17(1·41) in groups with and without suture respectively; P = 0·002). There were no differences in the perioperative and postoperative need for analgesics, postoperative wound complications or cervical scar cosmesis 6 months after surgery (mean(s.d.) POSAS 23·99(9·53) versus 26·51(8·69); P = 0·148). CONCLUSION: Omitting the platysma muscle suture after thyroid surgery resulted in less wound-specific pain initially, with no difference in postoperative wound complications or cosmetic results. Registration number: NCT02951000 (http://www.clinicaltrials.gov).

DYSMICROBISM, INFLAMMATORY BOWEL DISEASE AND THYROIDITIS: ANALYSIS OF THE LITERATURE.

The human body is colonized by a large number of microbes that are collectively referred to as the microbiota. They interact with the hosting organism and some do contribute to the physiological maintenance of the general good health thru regulation of some metabolic processes while some others are essential for the synthesis of vitamins and short-chain fatty acids. The abnormal variation, in the quality and/or quantity of individual bacterial species residing in the gastro-intestinal tract, is called “dysmicrobism”. The immune system of the host will respond to these changes at the intestinal mucosa level which could lead to Inflammatory Bowel Diseases (IBD). This inflammatory immune response could subsequently extend to other organs and systems outside the digestive tract such as the thyroid, culminating in thyroiditis. The goal of the present study is to review and analyze data reported in the literature about thyroiditis associated with inflammatory bowel diseases such as Ulcerative Colitis (UC) and Crohn’s Disease (CD). It was reported that similarities of some molecular bacterial components with molecular components of the host are considered among the factors causing IBD through an autoimmune reaction which could involve other non-immune cell types. The axis dysmicrobism-IBD-autoimmune reaction will be investigated as a possible etiopathogenic mechanism to Autoimmune Thyroiditis. If such is the case, then the employment of specific probiotic strains may represent a useful approach to moderate the immune system.

Endothelial progenitor cell mobilization by preoperative exercise: a bone marrow response associated with postoperative outcome.

BACKGROUND: Preoperative anaemia is associated with increased morbidity in patients undergoing major surgery. Whether erythrocytes are the only bone-marrow-derived cell lineage that associates with increased surgical complications is unknown. This prospective observational trial studied the mobilization of endothelial progenitor cells (EPCs) in response to exercise in association with postoperative complications. METHODS: After IRB approval, 60 subjects undergoing major thoracic surgery were exercised to exhaustion (peak V̇(O2)). Peripheral blood collected before and after peak exercise was quantified for EPC lineages by fluorescence-activated cell sorter analysis. Complication analysis was based on the Clavien-Dindo classification. RESULTS: Exhaustive exercise increased EPC [CD45-133+34+ cells=150 (0.00-5230) to 220 (0.00-1270) cells µl(-1); median change (range)=20 (-4,180-860) cells µl(-1); P=0.03] but not mature endothelial cell (EC) subpopulations. Pre-exercise levels [odds ratio (OR)=0.86, 95% confidence interval (CI): 0.37-2.00, P=0.72), change after exercise as a continuous variable (OR=0.95, 95% CI: 0.41-2.22, P=0.91) and a positive response after exercise (change >0 cells µl(-1); OR=0.41, 95% CI: 0.13-1.28, P=0.12) were not statistically significantly associated with the incidence of postoperative complications. Post-hoc receiver operating characteristic curve analyses revealed that subjects with a CD45-133+34+ increase ≥60 cells µl(-1) in response to exercise suffered fewer postoperative complications [86% sensitivity, 48% specificity and AUC=0.67 (95% CI: 0.52-0.81)]. CONCLUSIONS: Preoperative exercise induces EPC into the peripheral circulation. Subjects with a poor EPC response had a pre-existing propensity for postoperative complications. This warrants further research into the role of bone marrow function as a critical component to endothelial repair mechanisms. CLINICAL TRIAL REGISTRATION: IRB 2003-0434 (University of Texas M.D. Anderson Cancer Center, Houston, TX, USA).

Seasonal changes of C and N non-structural compounds in the stem sapwood of adult sessile oak and beech trees.

We assessed the pools of non-structural nitrogen compounds (NSNC) through a year, thereby addressing the question of whether mature sessile oak [Quercus petraea (Matt.) Liebl.] and beech (Fagus sylvatica L.), which differ in wood anatomy and growth patterns, exhibit contrasting seasonal dynamics of NSNC pools as previously shown for non-structural carbohydrate (NSC) pools. Seasonal fluctuations of NSNC (amino acids and soluble proteins) and NSC (starch and soluble sugars) pools were analyzed in the inner and the outer stem sapwood. In oak, NSC showed marked seasonal variation within the stem sapwood (accumulation during winter and decrease during bud burst and early wood growth), whereas in beech seasonal fluctuations in NSC were of minor amplitude. Even if the distribution and intensity of the NSNC pools differed between the two species, NSNC of the stem sapwood did not show seasonal variation. The most significant change in NSNC pools was the seasonal fluctuation of protein composition. In both species, two polypeptides of 13 kDa (PP13) and 26 kDa (PP26) accumulated during the coldest period in parallel with starch to sugar conversion and disappeared with the onset of spring growth. The absence of seasonal changes in total soluble protein concentration suggests that the polypeptides are involved in the internal nitrogen (N) cycling of the stem rather than in N storage and remobilization to the other growing organs of the tree.

Minimally invasive esophagectomy versus open esophagectomy, a symptom assessment study.

Minimally invasive esophagectomy (MIE) is used with hope to decrease the morbidity associated with an open esophagectomy. Reflux and dumping syndromes are the most important functional complaints in patients after esophagectomy. This study compares the functional benefits of MIE with open esophagectomy. The study enrolled patients who underwent either minimally invasive or open esophagectomy for cancer between 2004 and 2009. No patients in the MIE group had a pyloroplasty or myotomy. Each patient in the MIE group was paired to a patient in the open esophagectomy group via propensity matching. Matching variables included age, race, gender, preoperative treatment, history of prior cancer, American Society of Anesthesiologists Risk Scale, performance status, clinical stage, body mass index, histology, level of anastomosis, and time elapsed since surgery. The patients were asked to answer 26 questions about their reflux and dumping using validated questionnaires. A total of 181 patients were included in the study. From this group, 44 pairs of patients were created and used for the analysis. The median follow-up was 12.1 months for the MIE group and 18.3 months for the open group. The reflux score was slightly worse in the MIE group (5.5 versus 3.5, P= 0.021). There was no difference in the dumping symptoms between the two groups. The most common complaints seen in the dumping questionnaire in almost one-third of all patients were early satiety, abdominal discomfort, nausea, and diarrhea. Of the patients, 77% were satisfied or very satisfied with their condition in the MIE group compared with 93% in the open group (P= 0.287). Reflux, dumping, and overall satisfaction after MIE without pyloroplasty are comparable with those obtained after open esophagectomy with a pyloric drainage procedure.

Removal of Pb(II), Cd(II) and Co(II) from aqueous solution using Garcinia mangostana L. fruit shell.

This study examines the possibility of using mangosteen shell to remove low concentrations of lead, zinc and cobalt (less than 100 mg/l) from aqueous solution. It was found that the biosorption capacities were significantly affected by solution pH, contact time and initial metal ions concentration. Un-extracted and extracted dyes of mangosteen shell were investigated. Moreover higher pH up to 5 favoring higher metal ion removal. Kinetic and isotherm experiments were carried out at the optimal pH: at pH 5.0 for lead and zinc, and at pH 4.0 for cobalt. The metal removal rates were rapid, with 90% of the total adsorption taking place within 60 min. Mangosteen shell showed the highest potential for the removal of toxic metals in aqueous solution.

Gamma-radiation sensitivity and risk of glioma.

BACKGROUND: About 9% of human cancers are brain tumors, of which 90% are gliomas. gamma-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the gamma-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma. METHODS: We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We gamma-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. RESULTS: We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001). CONCLUSION: gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.

Risk assessment for developing gliomas: a comparison of two cytogenetic approaches.

Chromosome instability (CIN) measured as chromosome aberrations has long been suggested as a cancer susceptibility biomarker. Conventional cytogenetic end-points are now being improved by combining molecular methods, which increases the sensitivity, specificity, and precision of the assay. In this study we examined both spontaneous and gamma-ray induced CIN in lymphocyte cultures from 51 previously untreated glioma patients and 51 age-, sex- and ethnicity-matched controls. CIN was assessed using two parallel methods: (1) the mutagen sensitivity (MS) assay and (2) the multicolor fluorescence in situ hybridization (FISH) assay. The frequency of spontaneous breaks was significantly higher in glioma patients (mean+/-S.D., 2.12+/-1.07) than in controls (1.24+/-0.86, P<0.001) when using the FISH assay but not the MS assay (0.019+/-0.02 and 0.019+/-0.01, respectively; P=0.915). Similarly, the frequency of induced chromatid breaks was significantly higher using the FISH assay (3.39+/-1.72) but not the MS assay (0.42+/-0.16) in the patients versus controls (2.08+/-1.18 and 0.37+/-0.15, respectively; P<0.001 and P=0.10, respectively). By using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (ORs) of 5.13 (95% CI=2.23-12.1) for spontaneous and 4.86 (95% CI=2.08-11.4) for induced CIN using the FISH assay, whereas the ORs were 1.32 (95% CI=0.49-3.58) and 1.28 (95% CI=0.59-2.80) for spontaneous and induced CIN using the MS assay. There was also a significant increase in the frequency of hyperdiploid cells in the glioma cases which could only be detected using the FISH assay (OR=4.0, 95% CL=0.9-17.0). By combining both methods an estimated risk of 7.0 (95% CI=1.7-25.6) was observed. There was no correlation between the breaks detected by the two methods suggesting that each method is a measure of a different event. The results indicate that using the multicolor FISH assay for detection of CIN in peripheral blood lymphocytes in glioma patients is a more useful marker for risk assessment.

The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK.

DNA repair plays a critical role in protecting the genome of the cell from the insults of cancer-causing agents such as those found in tobacco smoke. Reduced DNA repair capacity would, therefore, constitute a significant risk factor for smoking-related cancers. Recently, a number of polymorphisms in several DNA repair genes have been discovered, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility in exposed populations. In the current study, we explored the relationship between two polymorphisms in the DNA repair gene XRCC1 (polymorphisms in codons 194 and 399) and the genotoxic response induced by the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The sister chromatid exchange (SCE) assay was used as a marker of genetic damage. Our results, using whole blood cultures from 47 volunteers, indicated that treatment of cells with 0.24, 0.72 and 1.44 mM of NNK induced a concentration-dependent increase in the mean number of SCE (P<0.001). There was a significant difference (P<0.05) in response to NNK treatment between cells from individuals with the 399Gln allele (either homozygous or heterozygous) and cells from individuals with the homozygous 399 Arg/Arg genotype. Treatment of cells that have the 399Gln allele with 0.24, 0.72 and 1.44 mM NNK resulted in 22.8, 35.8 and 52.8% increases in NNK-induced SCE, respectively. Treatment of cells with the 399 Arg/Arg genotype using the same NNK concentrations resulted in 16.0, 15.5 and 32.6% increases in NNK-induced SCE, respectively. In contrast, no significant difference in NNK-induced SCE was observed between cells with the codon 194 Arg/Arg genotype and cells with the codon 194 Arg/Trp genotype at all concentrations of NNK tested. These data suggest that the Arg399Gln amino acid change may alter the phenotype of the XRCC1 protein, resulting in deficient DNA repair. Our study underscores the important role of polymorphisms in DNA repair genes in influencing the genotoxic responses to environmental mutagens, and justifies additional studies to investigate their potential role in susceptibility to cancer.

Chromosome aberrations as a predictor of clinical outcome for smoking associated lung cancer.

The ability to identify individuals at greatest risk of developing lung cancer can significantly enhance the efficacy of intervention modalities. One strategy for identifying these individuals is through biomarkers that reflect the severity of their cancer. In the present study, we evaluated 22 lung cancer patients and 35 controls to determine whether the frequency of chromosome aberrations was significantly associated with specific clinical variables such as the histological type, grade and stage of the tumors. Chromosome aberrations (expressed as total breaks) were investigated on chromosome 1 in interphase nuclei obtained from blood lymphocytes of the study participants using the fluorescence in situ hybridization (FISH) chromosome aberration assay. Our results indicate a significant linear increase (P=0.01) in the level of breaks with respect to the grade of the carcinoma. The poorly differentiated tumors had a significantly higher level of chromosome breaks mean+/-SD (1.7+/-0.46) as compared to the well differentiated tumors (0.98+/-0.23, P<0.05). These results indicate that chromosome aberrations, as determined by the FISH assay, can be used as a biomarker for identifying individuals with aggressive types of lung cancer and potentially, as a predictor for prognostic outcome of the disease.

Increased chromosomal instability in peripheral lymphocytes and risk of human gliomas.

Brain tumors exhibit considerable chromosome instability (CIN), suggesting that genetic susceptibility may contribute to brain tumorigenesis. To test this hypothesis, in this pilot study, we examined for CIN in short-term lymphocyte cultures from 25 adult glioma patients and 28 age-, sex- and ethnicity-matched healthy controls (all Caucasian). We evaluated CIN by a multicolor fluorescence in situ hybridization assay using two probes: a classic satellite probe for a large heterochromatin breakage-prone region of chromosome 1 and an alpha satellite probe for a smaller region adjacent to the heterochromatin probe. Our results showed a significant increase in the mean number of spontaneous breaks per 1000 cells in glioma patients (mean +/- SD, 2.4+/-0.8) compared with controls (1.4+/-0.9; P < 0.001). By using the median number of breaks per 1000 cells in the controls as the cutoff value, we observed a crude odds ratio (OR) of 8.5 [95% confidence interval (CI) = 2.05-34.9, P < 0.001] for spontaneous breaks and brain tumor risk. After adjustment for age, sex and smoking status, the adjusted OR was 15.3 (95% CI, 2.71-87.8). A significant increase in cells with chromosome 1 aneuploidy (in the form of hyperdiploidy) (P < 0.001) was also observed in the glioma cases, with an adjusted OR of 6.6 (95% CI = 1.5-30, P < 0.05). These findings suggest that CIN can be detected in the peripheral blood lymphocytes of brain tumor patients and may be a marker for identifying individuals at risk.

Genetic polymorphism and their contribution to cancer susceptibility.

Since the majority of chemical carcinogens are not capable of causing hazardous effects per se, the metabolism of these compounds is a crucial part of the initial host response to the environmental exposure. Disturbances in the balance between activation and detoxification may thus explain the individual variations in responses to exposures to carcinogens. The amount of the ultimate carcinogen produced depends on the action of competing activation and detoxification pathways involving cytochrome P450 and glutathione-S-transferases enzymes.

Association of the NAT1*10 genotype with increased chromosome aberrations and higher lung cancer risk in cigarette smokers.

The NAT1 gene exhibits polymorphisms in the non-coding polyadenylation region with a number of alleles. Of these alleles, NAT1*10 is responsible for increased NAT1 enzyme levels and is reported to be associated with increased risk for colorectal and bladder cancers. In view of the possible role of the NAT1 gene product in the metabolism of a number of cigarette smoke carcinogens, we tested the possibility that genetic variation in the NAT1 gene might also be associated with increased risk for lung cancer. Allelic variances of the NAT1 gene were analyzed in 45 lung cancer patients and 47 controls who were matched with respect to age, race and gender using restriction fragment length polymorphism (RFLP) analysis and allele-specific (AS)-PCR. Our results indicate that individuals who inherited the NAT1*10 allele had a 3.7-fold increased relative risk for lung cancer (95% CL = 1.2-16.0, p < 0.02). There was a 6.8-fold increase in relative risk for lung cancer associated with the inheritance of the NAT1*10 allele in younger individuals (< 60 years of age) compared to 2.2-fold increase in older individuals (> 60 years old) (OR = 6.8; 95% CL = 1.1-40.7, p < 0.01 and OR = 2.2; 95% CL = 0.5-11.1, p = 0.2, respectively). We have also applied the sensitive fluorescence in situ hybridization (FISH) tandem probe assay to elucidate the frequency of chromosome breakage among a subgroup of the studied individuals harboring the NAT1*10 allele (17 lung cancer patients, 17 smoking controls and 7 non-smoking controls). Our results indicate a significant increase (p < 0.001) in the frequency of chromosome breaks in lung cancer patients (mean +/- SE per 100 cells = 1.45 +/- 0.11) and in smoking controls (1.30 +/- 0.13) compared to non-smoking controls (0.47 +/- 0.07). Regression analysis indicated a highly significant positive correlation between the duration of smoking in years and the frequency of chromosome breaks in lung cancer patients (r = 0.62, p = 0.008), but not in smoking controls (r = 0.02; p = 0.91). These findings suggest that NAT1 polymorphism may be an important genetic determinant of lung cancer risk. In addition, these data provide a mechanistic link between the inheritance of the NAT1*10 allele and smoking-induced lung cancer. Given that the NAT1 enzyme can mediate activation and detoxication pathways for numerous carcinogens and given that this polymorphism is prevalent in the general population (20-50% frequency), it may play a significant role in influencing the outcome of a variety of environmental cancers.

Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers.

Genotoxic effects linking cigarette smoking with lung cancer have not been consistently demonstrated, therefore claims for the cause-effect relationships are vigorously contested. Using matched populations of 22 lung cancer patients who have been cigarette smokers (LCP), 22 non-cancerous cigarette smokers (SC) and 13 non-smokers (NSC), we have applied the fluorescence in situ hybridization (FISH) tanden probe assay to elucidate the frequency of chromosome breakage among the participants. Two probes were used, a classical satellite probe which hybridizes to the large heterochromatin region of chromosome 1, and an alpha-satellite probe which targets a small region adjacent to the heterochromatin probe. The highest frequency of structural aberrations was observed in LCP (1.4 +/- 0.1) followed by SC (1.25 +/- 0.1) and NSC (0.4 +/- 0.1). Aberration frequencies were not significantly different between LCP and SC (p > 0.05), however, a statistically significant difference was detected between the smoker populations combined (LCP and SC) and the NSC (p < 0.001). The breakage frequencies showed a positive correlation with duration of smoking for LCP (r = 0.5; p < 0.01), but not for SC (P > 0.05). In addition, the aberration frequencies were influences by the inheritance of polymorphic glutathione S-transferase (GST) genes. LCPs missing one or the other GST (GSTM1 or GSTT1) genes were found to have significantly higher chromosome breaks compared to LCPs with both genes present (p < 0.05). Our data indicate that genetic predisposition and chromosome aberrations may be mechanistically related to the initiation of lung carcinogenesis; therefore, they may be useful biomarkers for lung cancer among cigarette smokers.

Polymorphism of metabolizing genes and lung cancer histology: prevalence of CYP2E1 in adenocarcinoma.

The relationship between genetic predisposition and development of specific cancers has not been adequately elucidated. In this study, the involvement of three polymorphic genes (CYP2E1, GSTM1, and GSTT1) in the development of different histological types of lung cancer was investigated. DNA was extracted from peripheral blood lymphocytes of lung cancer patients who have been long-term cigarette smokers (n = 52). Allelic variants of CYP2E1 were detected using PCR followed by PstI restriction enzyme digest and RFLP analysis, which detects a specific mutation causing over-expression of the gene. GSTM1 and GSTT1 genotypes were detected using two separate differential PCR methods. Our results indicate a 13.5% allele frequency for the CYP2E1 rare PstI site among the lung cancer patients which represents a 3.4-fold increase over the normal controls (OR = 3.5, 95% CL = 0.65-25.8). A novel observation is that all the patients with this polymorphism had adenocarcinomas only, resulting in a significant association between them (OR = 16.17, 95% CL = 0.95-73, P = 0.02). The frequency of the null GSTM1 gene was 42.3% among the lung cancer patients with no preferential tendency towards developing squamous cell carcinoma versus adenocarcinoma (OR = 1.10, 95% CL = 0.3-4.14, P = 0.5). The GSTT1 gene was absent in 21.1% of the patients with a non-significant tendency towards developing squamous cell carcinoma (OR = 1.23, 95% CL = 0.25-6.1, P = 0.5). Another important observation is the significant predominance of the three predisposing polymorphic alleles among the adenocarcinoma patients (OR = 3.4, 95% CL = 0.78-16.1, P = 0.05) compared with the squamous cell carcinoma patients. The results of this study indicate that the inheritance of several polymorphic metabolizing genes, particularly the CYP2E1 gene, contributes not only to the development of lung cancer but also to the development of specific types of cancer.

Interactions between genetic predisposition and environmental toxicants for development of lung cancer.

Significant interindividual variations in health outcome may be caused by the inheritance of variant polymorphic genes, such as CYP2D6 and CYP2E1 for activation, and GSTM1 and GSTT1 for detoxification of chemicals. However, mechanistic studies linking the inheritance of predisposing genes with genotoxic effects towards cancer have yet to be systematically conducted. We have studied 54 lung cancer patients and 50 matched normal controls, who have been cigarette smokers, to elucidate the role of polymorphic genes in cancer. Our data indicates that the inheritance of unfavorable CYP2D6, CYP2E1, and GSTT1 genes in strongly correlated with the smoking-related lung cancer. For heavy cigarette smokers (> 30 pack-years), the smoking habit is the strongest predictor of lung cancer risk irrespective of the inheritance of unfavorable metabolizing genes. For moderate to light smokers (< 30 pack-years), the genetic predisposition plays an important role for the risk (odds ratio = 3.46; 95% Cl = 0.46-40.2). Using a subgroup of the study population, we observed that cigarette smokers having the defective GST genes have significantly more chromosome aberrations as determined by the fluorescence-in-situ-hybridization (FISH) technique than smokers with the normal GST genes (P < 0.001). In conclusion, our study provides data to indicate that individuals who have inherited unfavorable metabolizing genes have increased body burden of toxicants to cause increased genetic damage and to have increased risk for cancer. Studies like ours can be used to understand the basis for interindividual variations in cancer outcome, to identify high risk individuals and to assess health risk.

Combined genetic polymorphism and risk for development of lung cancer.

Susceptibility to lung cancer has been shown to be modulated by host specific factors. Inheritance of different polymorphic cytochrome P450s (CYPs) and the glutathione S-transferases (GSTs) which affect metabolism of environmental toxicants may play a key role in individual susceptibility. Although individual polymorphic genes have been reported to be associated with development of lung cancer, little is known about the combined effects of several genes in carcinogenesis. From our study of 54 lung cancer patients and 50 matched controls, we observed that a combination of several versions of 'unfavorable' metabolizing genes (CYP2D6, CYP2E1, GSTM1 and GSTT1) is strongly associated with lung cancer. The relative risk for the different combinations of these genotypes ranged between 1.3 and 14, with higher risk involving the activating genes. The duration and intensity of heavy smoking (expressed in pack-years) are the most important determinant for the development of lung cancer. For example, the estimated risk for development of lung cancer associated with smoking > 30 pack-years is represented by an odds ratio = 6.65; 95% CL = 2.3-19.9 irrespective of an individual's genotype, whereas for smoking between > 30 and < 50 pack years, odds ratio = 4.5; 95% CL = 1.37-15; and for smoking > 50 pack-years, odds ratio = 30; 95% CL = 5.7-114. On the other hand, smoking of less than 30 pack-years is associated with an increased risk in the presence of the polymorphic genes (odds ratio = 2.5; 95% CL = 0.32-54). The results of our study indicate that the inheritance of multiple 'unfavorable' genotypes, especially activating genes, is a crucial predisposing factor for the development of lung cancer from cigarette smoking. In addition, the genes may cause moderate smokers who would normally outlive the deleterious effects of smoking to develop lung cancer. The information can therefore be used to target individuals for prevention of health problems.

Indirect photometric detection of inorganic anions in microcolumn ion chromatography using octadecylsilica immobilized with bovine serum albumin as stationary phase.

Octadecylsilica immobilized with bovine serum albumin was capable of separating inorganic anions. The stationary phase retained anions under acidic conditions, and the use of aqueous solution containing sodium iodide and tartaric acid as the eluent allowed the indirect photometric determination of chloride and nitrate in water and serum samples. The mobile phase conditions were optimized.