, 2008; Gotti et al., 2010; Tapper et al., 2004) but see (Yang et al., 2011). This is in contrast to the VTA where infusion of DH��E greatly attenuates nicotine self-administration (Corrigall et al., 1994). Other studies show that local infusion of an ��6��2*nAChR antagonist, ��-conotoxin PIA, (Dowell et al., 2003) into the VTA also attenuates they systemic administration of nicotine in rats that were previously trained for food (Gotti et al., 2010). Immunoprecipitation studies suggest that these receptors are ��4��6��2��3nAChRs (Gotti et al., 2010). Studies that use local self-administration of low-dose nicotine in the VTA of nicotinic subunit knockout mice reveal similar behavioral effects although intraVTA infusion of nicotine is attenuated to a greater extent in ��4 subunit knockout mice than in ��6 subunit knockouts (Exley et al.

, 2011), suggesting that within the VTA ��4��2*nAChRs without an ��6 subunit regulate intraVTA administration of nicotine (Exley et al., 2011). These studies also showed that VTA DA neuron activity using this regimen was specifically abolished in ��4KO mice (Exley et al., 2011) and not ��6KO subjects, suggesting that ��6��2*nAChRs exert their DA-releasing activity (Drenan et al., 2008) elsewhere in the mesolimbic circuitry, namely in the NAc or on terminals in the dorsal striatum (Champtiaux et al., 2003; Drenan et al., 2008; Exley et al., 2008; Gotti et al., 2010; Kulak et al., 1997; Meyer et al., 2008; Salminen et al., 2004, 2007). Evidence suggests that the nM concentrations of nicotine used in the intraVTA study, however, may preferentially desensitize rather than activate nAChRs (Fenster et al.

, 1999; Grady, Marks, & Collins, 1994; Grady, Wageman, Patzlaff, & Marks, 2012; Lester & Dani, 1995; Lu, Marks, & Collins, 1999; Marks, Grady, Yang, Lippiello, & Collins, 1994; Paradiso & Steinbach, 2003). Recent data suggest that ��6��2*nAChRs are persistently activated by 300 nM nicotine and in comparison with ��4��2*nAChRs, ��6��2*nAChRs are resistant to the desensitizing effects of low-dose nicotine (Grady et al., 2012; Liu, Zhao-Shea, McIntosh, Gardner, & Tapper, 2012). Whereas inhibition of ��6��2*nAChRs would be expected to reduce VTA DA activity, previous data using slice electrophysiology have shown that desensitization of ��4��2*nAChRs on GABA terminals in the VTA results in a disinhibition of DA receptors that may increase their sensitivity to further excitatory input (Mansvelder, Mertz, & Role, 2009; Mansvelder et al.

, 2002; Pidoplichko, DeBiasi, Williams, & Dani, 1997). Studies using systemic administration of independent compounds with antagonist activity at ��6��2*nAChRs have reported reductions of DA release and nicotine self-administration in rats (Markou & Paterson, 2001; Mogg et al., Drug_discovery 2002; Neugebauer, Zhang, Crooks, Dwoskin, & Bardo, 2006; Rahman et al., 2007).

Such a correspondence of reports, however, does not necessarily imply that this reported age is, in fact, accurate as both reports may be incorrect. Our results may have direct implications about choosing among alternative measures Fluoro-Sorafenib in analyses of tobacco use, for example, for estimating the total duration of smoking fairly regularly among former smokers. Given that the reliability of the age of initiation of fairly regular smoking (reported by former and current smokers), and that of the time since completely quitting smoking, were higher than the reliability for the number of years a former smoker smoked every day, our findings suggest that it may be preferable to construct the duration of total smoking by using the former two measures, rather than depending solely on former smokers�� direct reports of the number of years smoked every day��even allowing that there may be gaps of nonsmoking within this computed period for some people.

Future research on the reliability of survey reports of tobacco use can be targeted toward further examination of the odds of strict agreement, as a function of demographic or other respondent characteristics. For example, we observed that males were less likely to provide consistent answers than were females when reporting the time since completely quitting smoking. Therefore, it is essential to identify the underlying reasons for this observed gender effect, for example, it could be that males are more likely to satisfice than are females when answering smoking-related questions.

It is also important to investigate other criteria for defining agreement, such as through relaxing requirements for strict agreement (e.g., allowing a difference of up to 2 years between test and retest responses regarding the number of years smoked everyday by former smokers, when establishing matching rules). One problem with this type of relaxation, however, is that such a definition may not be reasonable across all population groups. For example, a 2-year difference in responses for older populations might not be as meaningful as it is for young adults. Thus, suitable definitions should be constructed with respect to subgroups if one wishes to examine the odds of such an agreement. In addition, it would be of interest to investigate factors that may contribute to the odds of producing highly contradictory responses at two time points.

There could be a set of sociodemographic, smoking behavioral, or survey administration characteristics associated with response discordance. For example, it might be the case that more cigarettes smoked per day, more Batimastat discrepant responses about the number of cigarettes smoked per day are provided. For never smoked reporting, it could be the length of time since completely quit smoking among former smokers that effects the reliability of reporting former versus never smoking.

Statistical analysis. Data are expressed as means with SDs or SEMs, as indicated in the text. In the BSEP inhibition screen, compounds that significantly selleck chemical Bicalutamide decreased BSEP transport were identified by 1-way ANOVA with Bonferroni��s post hoc test, as implemented in Prism 5 (GraphPad Software, Inc, La Jolla, CA). Differences in the proportions of DILI-inducing agents in each ADR class were determined using normality tests. The Marascuillo procedure was used to determine statistical differences of mild and severe DILI distribution in the different ADR sections. Analysis of SCHH accumulation data were conducted using 2-way ANOVA with Bonferroni��s post hoc test. RESULTS TA Transport in Inverted Membrane Vesicles To investigate the impact of drugs on BSEP-mediated TA transport, we used inverted membrane vesicles from cells overexpressing human BSEP.

This system allows direct measurement of drug interactions with BSEP, thereby eliminating certain confounding factors that affect whole-cell systems (such as drug metabolism and the need for sufficient membrane permeability to reach transporter binding sites). The ATP-dependent transport of TA into inverted membrane vesicles was linear for up to 15min (Fig. 2A). The passive TA transport was approximately 5% of the active uptake under the conditions applied. The kinetics of the TA transport was determined from the data in Figure 2B using nonlinear regression. This resulted in a K m of 17.8��5.0��M and a V max of 286.2��28.2 pmol/mg protein/min, in good agreement with previously published data (Kis et al., 2009; Yabuuchi et al.

, 2008). Two inhibitors (cyclosporine A and indocyanine green) were used as controls throughout the experiments and gave low interday (n = 45) variability of 6% and 7%, respectively. Indocyanine green and cyclosporine A inhibited TA uptake with IC50 values of 3.7��1.3 and 4.6��1.2��M, respectively, as determined by fitting a sigmoidal dose-response relationship to the inhibition data (Figs. 2C and and2D2D). FIG. 2. Kinetics of taurocholate (TA) transport in bile salt export pump (BSEP)�Coverexpressing inverted Sf9 membrane vesicles. A, Linearity of TA transport. The TA transport kinetics was linear up to 15min (squares). At 5-min incubation (used in the BSEP … Inhibition of BSEP Transport in Inverted Membrane Vesicles Of the 250 compounds screened for inhibition of TA transport, 86 were identified to significantly (p < .

05) inhibit BSEP at 50��M (Fig. 3). Thirty-seven of these have, to our knowledge, not been previously reported (Table 2). No transport stimulation was detectable at the statistical significance level used (p < .05). Among Brefeldin_A the 86 inhibitors, 53 reduced BSEP-mediated TA transport by more than 50% compared with the controls (without inhibitor) and were therefore defined as strong inhibitors (as described in the Materials and Methods section).

M: Methylated site; U: Unmethylated … Re-expression of CD133 after treatment with 5-aza-2��-deoxycytidine To confirm whether the differential CD133 expression was related to DNA methylation, 11 cell lines with undetectable or low expression inhibitor Dorsomorphin of CD133 were treated with 5-aza-2��-deoxycytidine. The treatment recovered CD133 expression in four of the weakly CD133 expressing cell lines (SNU-61, SNU-769A, SNU-C4 and Colo320) and two cell lines without detectable CD133 expression (Figure (Figure5A).5A). However, 5-aza-2��-deoxycytidine treatment did not significantly influence CD133 gene expression in SNU-503, HCT-8, LS174T, NCI-H716 and SW1116 cell lines. Examination of CD133 expression by real- time PCR revealed that CD133 expression was increased after 5-aza-2��-deoxycytidine treatment in SNU-503, HCT-8, LS174T and SW1116 cell lines (Figure (Figure5B),5B), and decreased in the NCI-H716 cell line.

Figure 5 Expression analysis after treatment with 5-aza-2��-deoxycytidine (5-Aza). A: RT-PCR analysis of CD133 expression in 11 cell lines with or without 5-aza-2��-deoxycytidine treatment; B: Representative results of real-time PCR analysis revealing … DISCUSSION It has been postulated that CSCs are able to maintain tumor bulk due to the abilities of self-renewal and differentiation into cells with low potential. CD133 is one of CSC markers in colorectal carcinoma and CD133-positive cells in colon cancer exhibit a high tumorigenic ability in vivo. In a previous study, the CD133-positive cells separated from tumors were able to form tumor bulk in the immuno-compromised mouse models with less numbers than the CD133-negative cells and these cells showed a long-term tumorigenic potential[4].

Furthermore, CD133-positive cells in colon cancer cell lines showed higher levels of proliferation, colony formation and invasive ability in vitro than CD133-negative cells[19]. Presently, CD133 was down-regulated in 11 of the 32 colorectal cancer cell lines. Since abnormal DNA methylation of CD133 gene is related to CD133 expression in colorectal tumors[20], we hypothesize that CD133 expression is regulated by hypermethylation of the promoter region in this gene, and analyzed promoter methylation status of the CD133 gene with a methylation-specific PCR after sodium-bisulfite modification and by clonal sequencing analysis.

A methylation analysis of promoters P1 and P2 in cell lines demonstrated tissue specificity of the promoter P2 methylation and practically no specificity in the methylation of the P1 promoter[11]. Therefore, we designed the primers with promoter P2 sequences for MS-PCR and bisulfite sequencing analysis and sequencing primers containing 32 of CpG dinucleotides (Figure (Figure1B1B). Methylation of the CD133 gene promoter was observed in 13 cell lines (SNU-503, SNU-1047, Carfilzomib SNU-C2A, SNU-C4, Caco-2, DLD-1, HCT-15, HCT116, LoVo, LS174T, NCI-H716, SW403 and SW1116).

1 mL, 0.5 mg?mL?1, Sigma Chemical Co.) enabled analysis of leucocyte�Cendothelium interactions in the microvascular bed. For observations of the microcirculation, we used a modified Olympus contain microscope (BX50WI, Olympus Optical Co. GmbH, Hamburg, Germany) and recorded videos on a computer for later off-line analysis of leucocyte-endothelium interactions. Twenty-five C57BL/6 wild-type and five LFA-1 gene-targeted male mice were used, two to six postcapillary venules were evaluated in each animal and leucocyte rolling was measured by counting the number of cells rolling along the endothelial lining for 20 s and is expressed as cells?min?1. Leucocyte adhesion was measured by counting the number of cells that adhered and remained stationary for more than 30 s during the observation time and is expressed as cells?mm?2.

Certain animals received an anti-P-selectin antibody (40 ��g, i.v., clone RB40.34, BD Biosciences Pharmingen) immediately before capturing microphotographs of the postcapillary venules in the pancreas in order to abolish leucocyte rolling and thereby enable visualization of the remaining leucocytes that were firmly adherent to the endothelium. Statistics Data are presented as mean values �� SEM. Statistical evaluations were performed by using non-parametrical tests (Mann�CWhitney). P < 0.05 was considered significant and n represents the number of animals. Results Role of LFA-1 in taurocholate-induced tissue damage in the pancreas First, we examined LFA-1 expression at the mRNA and protein level in the LFA-1 gene-targeted mice used herein and found that these animals completely lacked LFA-1 (Figure S1).

Retrograde infusion of sodium taurocholate into the pancreatic duct enhanced serum amylase levels by nearly 16-fold (Figure 1). Taurocholate-induced serum levels of amylase were reduced by more than 70% in LFA-1-deficient animals and in mice treated with an antibody against LFA-1 (Figure 1). Tissue damage was evaluated by quantification of acinar cell necrosis, oedema formation and haemorrhage in the pancreas. Taurocholate-induced acinar cell necrosis, oedema formation and interstitial haemorrhage were markedly attenuated in LFA-1 gene-targeted animals and in mice treated with the anti-LFA-1 antibody (Figure 2).

Moreover, morphological examination of the pancreas revealed normal microstructure in control animals, whereas taurocholate challenge caused severe Dacomitinib destruction of the pancreatic tissue structure characterized by extensive cell necrosis, oedema and massive infiltration of neutrophils (Figure 3). However, the structure of the pancreas was protected in LFA-1-deficent and in anti-LFA-1 antibody-treated mice challenged with taurocholate (Figure 3). Figure 1 Serum amylase (��Kat?L?1) in wild-type (WT) and lymphocyte function antigen-1 (LFA-1)-deficient mice. Pancreatitis was induced by infusion of sodium taurocholate into the pancreatic duct. Control mice received saline alone. Certain …

Cells were washed twice with PBS-HEPES between all blocking and staining steps and resuspended in PBS with 1% formalin prior to analysis. selleck compound To confirm the specificity of lectins, cells were pretreated with 1 U per ml of neuraminidase (NA) from Clostridium perfringens (Sigma) for 1 h prior to the avidin/biotin block. Samples were analyzed on a BD Facscalibur or BD LSR II (BD Biosciences), and a minimum of 5,000 events were recorded. Viruses and viral titration. Stocks of A/New Caledonia/20/99 (H1N1) and A/Wisconsin/67/05 (H3N2) viruses were kindly provided to San Raffaele Hospital (HSR) by Nadia Naffakh, Pasteur Institute, CNR Virus Influenza (Paris, France), and were serially expanded 2 times in MDCK cells prior to use.

To propagate IAV, monolayer-cultured MDCK cells were washed twice with PBS and infected with A/NewCaledonia/20/99 (H1N1) or A/Wisconsin/67/05 (H3N2) at a multiplicity of infection (MOI) of 0.001. After virus adsorption for 1 h at 35��C, the cells were washed twice and incubated at 35��C with Dulbecco’s modified Eagle’s medium (DMEM) without serum supplemented with tosylsulfonyl phenylalanyl chloromethyl ketone (TPCK)-treated trypsin (1 ��g/ml; Worthington Biomedical Corporation, Lakewood, NJ). Supernatants were recovered 48 h postinfection. LPAI H7N1 A/turkey/Italy/3675/1999 and H7N3 A/turkey/Italy/2962/2003 viruses isolated during epidemics in Italy were grown in 9-day-old embryonated SPF chicken eggs as described above. The sequences for A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2), and A/turkey/Italy/3675/1999 (H7N1) isolates were previously published.

For viral titration, plaque assays were performed as previously described (28). Briefly, MDCK monolayer cells, plated in 24-well plates at 2.5 �� 105 cells/well, were washed twice with DMEM without serum, and serial dilutions of virus were adsorbed onto cells for 1 h. The cells were covered with 2�� minimal essential Brefeldin_A medium (MEM)-Avicel (FMC Biopolymer, Philadelphia, PA) mixture supplemented with TPCK-treated trypsin (1 ��g/ml). Crystal violet staining was performed 48 h postinfection, and visible plaques were counted. Virus replication kinetics in pancreatic-cell lines. Semiconfluent monolayers of HPDE6 and hCM cells seeded on 24-well plates were washed twice with PBS and then infected with human viruses (H1N1 and H3N2) at an MOI of 0.001 and with avian viruses (H7N1 and H7N3) at an M.O.I of 0.01 using 200 ��l of inoculum per well. The inoculum was removed after 1 h of absorption and replaced with 1 ml of serum-free medium containing 0.05 ��g/ml TPCK-trypsin (Sigma).

Furthermore, unraveling these strategies mounted by the parasites to cooperate with the resident microbiota will allow a better understanding of co-evolution of host-pathogen interactions. Materials and Methods Ethics statement All procedures involving human subjects used in this study Tofacitinib Citrate order were approved by the Cameroonian national ethical committee (statement 099/CNE/SE/09). The gametocyte carrier used in this study was enrolled as a volunteer after his parents had signed a written informed consent. Mosquito collection and sample characterization A. gambiae mosquitoes were sampled in aquatic habitats at the L4 and pupae stages in four localities in Cameroon using standard dipping technique [75]. In each locality, breeding sites were inspected visually for presence of larval stages.

At each breeding site, 10 dips were taken with a standard dipper (300 ml) and kept in a 5-liter container for trans
Arsenic trioxide (ATO) which has been used for more than 2,000 years in Chinese traditional medicine for treatment of almost every disease has made a remarkable comeback into classical medicine after its high efficacy for treatment of acute promyelocytic leukemia (APL), reported by Chinese doctors, had been confirmed by the results from randomized clinical trials in Europe and the United States [1]�C[3]. The impressive complete remission and survival rates observed in APL prompted the subsequent testing of ATO also in other neoplastic diseases.

These studies revealed that besides specifically targeting the promyelocytic leukemia gene product (PML) and the APL-specific fusion protein of PML with the retinoic acid receptor alpha (PML-RAR-a) thereby promoting cell differentiation of leukemia cells, ATO can interfere with mitochondrial functions, the cellular redox system, the cell cycle and apoptosis. Since these cellular functions are generally involved in the response of tumor cells to ionizing radiation the radiosensitizing efficacy of ATO was subsequently evaluated. The first report of a synergistic activity of ATO in combination with radiotherapy came from a murine solid tumor model [4] and these early promising results were subsequently confirmed in xenograft models of glioma [5], [6], fibrosarcoma [7], cervical cancer [8] and oral squamous cell carcinoma [9]. Of note, despite its radiosensitizing activity in tumor tissue the addition of ATO to radiotherapy did not result in a significant increase in normal tissue toxicity [4], [9].

As predictive biomarker for enhanced pro-apoptotic and growth-inhibitory activity of ATO structural defects in the p53 gene have originally been described in models of B-cell lymphoma [10] and multiple myeloma [11], [12] which could also explain the low toxicity profile in normal cells expressing wildtype Drug_discovery (wt) p53.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Autoantibodies with high avidity and in high concentration are usually detected in sera of patients with Navitoclax cost systemic autoimmune diseases, and indicate tolerance breakdown. The strict association of some autoantibodies with certain diseases has granted them the reputation of specific biomarkers [1], [2], [3], [4]. The identification of a novel autoantibody associated with a given disease may contribute to the understanding of its pathophysiology and may enrich the array of diagnostic tests for that disease [2]. The standard method for autoantibody screening is the indirect immunofluorescence assay on HEp-2 cells (IIF-HEp-2), historically known as the antinuclear antibody ANA test.

However, a positive IIF-HEp-2 test is also observed in some patients with infectious and malignant diseases, as well as in up to 13% of healthy people [4], [5], [6]. A positive IIF-HEp-2 test has been reported in 7 to 50% of patients with HCV [7], [8], [9], [10], [11]. The few studies reporting on the immunofluorescence pattern of IIF-HEp-2 test in HCV patients have emphasized the nuclear fine speckled pattern and cytoplasmic fibrillar pattern [8], [9], [10], [12], [13]. Most IIF-HEp-2 reactivity in HCV patients is not associated with autoantibodies traditionally related to specific autoimmune diseases. However, a small fraction of HCV patients do present well characterized autoantibodies conventionally associated with autoimmune hepatitis, such as anti-LKM and anti-smooth muscle antibodies [14], [15], [16].

Anti-LKM antibody is classically associated with type 2 autoimmune hepatitis, but it has been observed in up to 10% of HCV patients, mostly males, and it appears to indicate mild liver histological and biochemical alterations in these patients [15], [17]. Anecdotal reports suggest that interferon-�� therapy may worsen inflammatory liver activity and increase serum enzyme in LKM-reactive HCV patients [17], [18]. Anti-smooth muscle antibodies are directed mostly to the polymerized form of actin and are traditionally associated with type 1 autoimmune hepatitis, but they can also be observed in a small fraction of HCV patients, usually at a lower titer than in autoimmune hepatitis [16].

HCV patients presenting anti-smooth muscle autoantibodies appear not to differ from those without these autoantibodies concerning clinical profile and response to treatment [15], [19]. Recently a novel IIF-HEp-2 cytoplasmic pattern has been reported in HCV patients [20], [21], [22], [23], [24], [25]. It is characterized by a variable number of 3�C10 ��m long rods and 2�C5 ��m diameter rings spread throughout the cytoplasm. Accordingly, the novel IIF-HEp-2 pattern has been designated the ��rods and rings�� (RR) pattern. Interestingly, not all commercial GSK-3 HEp-2 slides are appropriate for the observation of the RR pattern.

In some experiments, mice selleck chemicals were injected intraperitoneally with soluble gp130-FC fusion protein (sgp130Fc, 0.5 mg/kg; R&D Systems, Minneapolis, MN, USA) or phosphate-buffered saline (PBS). All surgical and experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) in College of Medicine, Seoul National University. Isolation of Colonic Epithelial Cells CECs were isolated using a modified version of previously described methods [60], [61]. In brief, colon pieces were incubated in Ca2+- and Mg2+-free Hanks Balanced Salt Solution (HBSS; Sigma Chemical) containing 2% calf serum at 37��C for 30 min while stirring. After collecting the supernatant, remaining tissue was resuspended in HBSS with 3 mM ethylenediaminetetraacetic acid (EDTA).

The tissues were incubated while stirring at 37��C for 30 min. The supernatant was then collected and centrifuged at 300��g for 10 min. Histopathology and Immunohistochemistry of Colon Tissue Large intestine specimens were fixed in 10% neutralized formalin for 24 h, embedded in paraffin, and sectioned at 4 ��m. Colon sections were stained with hematoxylin and eosin (H&E) for histopathological analysis, and stained immunohistochemically as described previously to investigate the expression of phospho-STAT3 (STAT3PY705) [62]. Briefly, paraffin-embedded slides were hydrated with ethanol and distilled water, followed by antigen retrieval in 10 mM sodium citrate buffer. Sections were incubated with anti-S100A9 (Abcam, Cambridge, MA, USA) and anti-STAT3PY705 immunoglobulin G (IgG; Cell Signaling Technology, Danvers, MA, USA) and stained with 3,3-diaminobenzidine substrate.

Image acquisition and processing were performed using a Leica microscope and the Leica Application Suite (Leica Microsystems, Buffalo Grove, IL, USA). Immunofluorescence of Colon Tissue To perform immunofluorescence analyses, mouse large intestine specimens were embedded in optimal cutting temperature compound (Sakura Finetek Japan, Tokyo, Japan) and sectioned at 10 ��m by cryostats (Leica Microsystems). The sections were incubated with a combination of anti-Gr-1-biotin and purified anti-CD11c antibodies (BD Biosciences) or with rabbit anti-STAT3PY705 IgG at 4��C overnight, followed by incubation with appropriate secondary antibodies. Stained sections were mounted in VectaShield 4��, Entinostat 6-diamidino-2-phenylindole (DAPI) mounting medium (Vector Laboratories, Burlingame, CA, USA) and analyzed under a confocal laser scanning microscope (LSM 510; Carl Zeiss, Gottingen, Germany). Images were taken under a confocal microscope using a 40�� objective.

27 In their study, Tsai et al28 found that vehicle selleck kinase inhibitor exhaust significantly influenced the total PAH exposure (11.4 ��g/m3). Urinary 1- hydroxypyrene levels in both mechanics and fuel attendants (3.02 ug/mol creatinine) at a Taiwan highway toll station were significantly higher than those of controls (0.41 ug/mol creatinine).28 In 2003, Bartimaeus and Jacobs showed that considerable exposure to petrol or its products over a long period of time could cause nephrotoxicity in motor mechanics.29 Kuusimaki et al30 found high concentrations of 1-hydroxypyrene in bus-garage workers and waste collectors (0.125 ��g mol/mol creatinine) when compared with controls (0.055 ��g mol/mol creatinine).31 Autrup et al reported higher urinary 1- hydroxypyrene level for suburban/rural bus drivers (0.25 ��g mol/mol creatinine).

32 Burgaz et al have reported a higher urinary 1-hydroxypyrene levels in taxi drivers (0.57 ��g mol/mol creatinine).33 Other researchers have also reported higher urinary 1- hydroxypyrene in professional drivers (0.181 ��g mol/mol creatinine) and commercial drivers (0.263 ��g mol/mol creatinine).33 From our findings, none of the three personal factors (age, work experience, and smoking habit) had a significant effect on predicting urinary 1- hydroxypyrene level in the different occupations. The highest concentration of 1-OHP was recorded in a 28-year-old fuel attendant with just 8 years working experience and no smoking history (Table 3) while a 60-year-old subject with 40 years exposure had no trace of urinary 1-hydroxypyrene.

Smoking is the most widely studied confounder of environmental and occupational PAH exposure studies and the most preventable risk factor for lung cancer,34 coronary heart disease,35 and chronic obstructive pulmonary disease.36 Overall, our study showed no significant correlation between cigarette smoking and increased urinary 1-hydroxypyrene of all three occupations. In this study, 1-hydroxypyrene was detected in only 20% of smokers. Several researchers found cigarette smoking to be correlated with an elevated urinary 1-hydroxypyrene. Merlo et al37 found that the average urinary 1-hydroxypyrene for smoking traffic officers (0.201 ��g mol/mol creatinine) was higher than their non-smoking counterparts (0.102 ��g mol/ mol creatinine) and Chuang et al reported that smoking office employees also had higher 1-OHPY levels (0.179 ��g mol/mol creatinine) when compared with their non-smoking counterparts (0.067 ��g mol/ mol creatinine).31 Ichiba et al38 reported a decrease in urinary 1-hydroxypyrene and 2-naphthol after smoking cessation. A study by Carmella and co-workers in 200939 also showed that smoking cessation among 17 Brefeldin_A smokers at various times corresponded to a decrease in their 1-hydroxypyrene concentrations.