[Differential proteomic screening of plasma exosomes before and after magnesium isoglycyrrhizinate treatment in chronic hepatitis B].

Objective: To screen the differential proteomic of plasma exosomes before and after magnesium isoglycyrrhizinate (MgIG) treatment in chronic hepatitis B patients. Methods: Plasma samples were collected from 36 cases with chronic hepatitis B before and after MgIG treatment (2 ml/case). Plasma exosomes were extracted by ultracentrifugation. Exosomal particles concentration and inner diameter were detected by Nanosight NS300 particle size analyzer. Three cases of plasma exosomes were randomly selected before and after MgIG treatment. Proteins were extracted after lysis and digested with trypsin. Label-free differential proteomics analysis was performed by liquid chromatography-tandem mass spectrometry to screen out differential proteins that changed more than 1.5 times. Enzyme linked immunosorbent assay (ELISA) was used to verify the quantitative differential protein expression (n = 30). Measurement data were compared by paired sample t-test. Results: The average particle concentration of the extracted exosomes was 2.2×10(9)/ml, and the average size was (107 ± 52) nm, which was consistent with the theoretical value of plasma exosome size, proving that the plasma exosomes were successfully extracted. Proteomics results showed that before and after MgIG treatment in chronic hepatitis B patients, a total of 153 differentially expressed proteins were screened, including 85 up-regulated and 68 down-regulated proteins. Enzyme-linked immunosorbent assay results showed that compared with the MgIG before and after treatment group of chronic hepatitis B patients, the differences in the concentrations of hepatocyte growth factor activator and hepatocyte growth factor like protein in plasma exosomes were statistically significant (P < 0.05). Hepatocyte growth factor activator concentration in the plasma exosomes before and after MgIG treatment group was (45.9 ± 9.4) µg/ml and (13.9 ± 2.0) µg/ml, respectively, and it was down-regulated by about 3 times. Hepatocyte growth factor-like protein concentration in the plasma exosomes before and after MgIG treatment group was (23.4 ± 4.9) µg/ml and (13.8 ± 2.2) µg/ml, respectively, and it was down-regulated by about 2 times. Enzyme-linked immunosorbent assay results had consistency with the proteomics results. Conclusion: This study successfully screened the differential proteomic of plasma exosomes before and after MgIG treatment in chronic hepatitis B, and provided experimental basis for studying the molecular mechanism of MgIG treatment for chronic hepatitis B.

Preoperative Evaluation of Patients with Hemifacial Spasm by Three-dimensional Time-of-Flight (3D-TOF) and Three-dimensional Constructive Interference in Steady State (3D-CISS) Sequence.

PURPOSE: The purpose of this study was to investigate and evaluate the accuracy and the preoperative diagnostic value of high-resolution magnetic resonance imaging (MRI) techniques, three-dimensional time-of-flight (3D-TOF) and three-dimensional constructive interference in steady state (3D-CISS) sequence, solely or in combination for the detection of the relationship between the facial nerve and adjacent vessels in patients with hemifacial spasm (HFS). METHODS: A total of 95 patients with primary HFS were subject to 3D-TOF and 3D-CISS MRI. The MR images were then used to evaluate the anatomical neurovascular relationships, and the results were compared with the surgical findings. We categorized the neurovascular relationship into three types: compression, contact, and neighboring or distant. Compression and/or contacts between root exit zone (REZ) and vessels were defined as positive, whereas neighboring or distant was considered to be negative. RESULTS: 3D-TOF combined with 3D-CISS assessment showed that 94 of 95 patients had artery compression or contact at REZ, whereas the remaining patient had compression at the peripheral branch of the facial nerve but not at REZ. The positive rates and the overall accuracy were 98.95 and 100 %, respectively, for the 3D-TOF combined with 3D-CISS assessment; 92.63 and 93.68 %, respectively, for the 3D-TOF assessment; and 85.26 and 86.32 %, respectively, for the 3D-CISS assessment. The positive rates and overall accuracy for the 3D-TOF combined with 3D-CISS assessment was significantly higher than those for the 3D-TOF or 3D-CISS assessment. CONCLUSIONS: Combination of 3D-TOF with 3D-CISS imaging well delineates the relationship between the facial nerve and adjacent vessels in terms of increased positive rates and accuracy.

Non-covalent doping of graphitic carbon nitride with ultrathin graphene oxide and molybdenum disulfide nanosheets: an effective binary heterojunction photocatalyst under visible light irradiation.

A proof of concept integrating binary p-n heterojunctions into a semiconductor hybrid photocatalyst is demonstrated by non-covalent doping of graphite-like carbon nitride (g-C3N4) with ultrathin GO and MoS2 nanosheets using a facile sonochemical method. In this unique ternary hybrid, the layered MoS2 and GO nanosheets with a large surface area enhance light absorption to generate more photoelectrons. On account of the coupling between MoS2 and GO with g-C3N4, the ternary hybrid possesses binary p-n heterojunctions at the g-C3N4/MoS2 and g-C3N4/GO interfaces. The space charge layers created by the p-n heterojunctions not only enhance photogeneration, but also promote charge separation and transfer of electron-hole pairs. In addition, the ultrathin MoS2 and GO with high mobility act as electron mediators to facilitate separation of photogenerated electron-hole pairs at each p-n heterojunction. As a result, the ternary hybrid photocatalyst exhibits improved photoelectrochemical and photocatalytic activity under visible light irradiation compared to other reference materials. The results provide new insights into the large-scale production of semiconductor photocatalysts.

Association between dental caries and obesity in preschool children.

AIM: The purpose of this study was to investigate the association between dental caries and obesity in preschool children. MATERIALS AND METHODS: A total of 329 preschool children were recruited from nine day care centers. A qualified dentist examined the oral health of each child and a caries score was recorded. Anthropometric measurements included body weight, height, triceps skinfold thickness, and body fat. Body mass index, and weight-for-height index were calculated. Parents or guardians answered a questionnaire regarding their children's dietary patterns, oral hygiene habits, and medical history, as well as parental practices and attitudes towards their children's oral health. RESULTS: The prevalence of dental caries was 73% in this study. Fourteen percent of the children were overweight or obese. The caries scores were not significantly different according to weight-for-height index categories. After taking into account important factors in the multiple regression models, body mass index and weight-for-height index, respectively, were not significantly associated with dental caries. CONCLUSION: This study showed that obesity was not significantly associated with dental caries in preschool children.

Overactive bladder in Taiwanese women: re-analysis of epidemiological database of community from 1999 to 2001.

AIMS: To update our previous computerized epidemiological data according to the new taxonomy, we re-evaluated and re-analyzed the data using the current definitions of lower urinary tract symptoms (LUTS) which were approved and published by the ICS in 2002 and 2010 according to patient perception. Further, we divided overactive bladder (OAB) symptoms into OAB dry and OAB wet to assess their prevalence percentages by using the current definitions. METHODS: OAB syndrome in our computerized database was re-defined as having the following storage symptoms present, that is, frequency, urgency, nocturia, urgency incontinence, or stress urinary incontinence (SUI). The prevalence of OAB syndrome was determined with a different taxonomy for those five storage symptoms either singly or in combination. OAB symptoms which were probably associated with mixed incontinence were either ignored or excluded. RESULTS: The prevalence of OAB syndrome varied from 34.76% to 28.33% to 20.95% using different classifications of the above five storage symptoms. The prevalence of OAB wet symptoms increased with advancing age and this finding was consistent with three different definitions. CONCLUSIONS: The prevalence of OAB using the current definition is slightly higher than the result found in our previous published data using a defective classification system of OAB symptoms. The effects of mixed symptoms and probable misclassification cannot be overlooked because many women with OAB (with or without urgency incontinence) might also have SUI.

Identification of cytoplasm types in rapeseed (Brassica napus L.) accessions by a multiplex PCR assay.

Cytoplasmic male sterility (CMS) has widely been used as an efficient pollination control system in rapeseed hybrid production. Identification of cytoplasm type of rapeseed accessions is becoming the most important basic work for hybrid-rapeseed breeding. In this study, we report a simple multiplex PCR method to distinguish the existing common cytoplasm resources, Pol, Nap, Cam, Ogu and Ogu-NWSUAF cytoplasm, in rapeseed. Cytoplasm type of 35 F(1) hybrids and 140 rapeseed open pollinated varieties or breeding lines in our rapeseed breeding programme were tested by this method. The results indicated that 10 of 35 F(1) hybrids are the Nap, and 25 the Pol cytoplasm type, which is consistent with the information provided by the breeders. Out of 140 accessions tested, 100 (71.4%), 21 (15%) and 19 (13.6%) accessions possess Nap, Cam and Pol cytoplasm, respectively. All 19 accessions with Pol cytoplasm are from China. Pedigree analysis indicated that these accessions with Pol cytoplasm were either restorers for Pol CMS, including Shaan 2C, Huiyehui, 220, etc. or derived from hybrids with Pol CMS as female parent. Our molecular results are consistent with those of the classical testcross, suggesting the reliability of this method. The multiplex PCR assay method can be applied to CMS "three-line" breeding, selection and validation of hybrid rapeseed.

Analysis of MS2Bnap genomic DNA homologous to MS2 gene from Arabidopsis thaliana in two dominant digenic male sterile accessions of oilseed rape (Brassica napus L.).

PCR technique was employed to isolate gene homologous to the MS2Bnap (X99922.1) from two rapeseed (Brassica napus L.) dominant digenic male sterile lines, namely 220A (male sterile) and 220B (male fertile), 6A (male sterile) and 6C (male fertile). The isolated 2,581 bp sequences from 220A (named 220A-gDNA, GenBank accession number AY288778), 220B (220B-gDNA, AY257490), 6A (6A-gDNA, DQ060318) and 6C (6C-gDNA, DQ060319) all contained six introns. Forty-one single nucleotide polymorphism (SNP) sites were detected by alignment of these four sequences, seven of them dispersed in the exon regions. Two SNPs (1247, 1656) were detected between 220A-gDNA and 220B-gDNA, and the one at nucleotide 1247 of 220A-gDNA with A replaced by C was a missense mutation, which may be the putative male sterility site in 220A. All eight SNPs identified between 6A-gDNA and 6C-gDNA were located in the third intron, so the proteins encoded by them are the same. The one SNP between 6A-/6C-gDNA and 220A-/220B-gDNA at nucleotide 2474 of 220A-/220B-gDNA with C replaced by G was a missense mutation. Mutation site of BNMS2PROT (CAA68190.1) encoded by MS2Bnap in 220A(254) and 6A/6C(584) is different, which indicated dominant digenic male sterile line 220AB and 6CA have some difference in the molecular level. Comparison of structure of MS2Bnap in B. napus with that of MS2 in Arabidopsis thaliana revealed that the similarity of exons between these two genes is higher than that of introns.

Transvascular dissemination of Porphyromonas gingivalis from a sequestered site is dependent upon activation of the kallikrein/kinin pathway.

BACKGROUND AND OBJECTIVE: Epidemiological evidence implicates a connection between human periodontitis and systemic diseases. One possible mechanism involves the direct dissemination of periodontopathogens to the target organs through the circulation. The aim of this work was to define the mechanism used by Porphyromonas gingivalis for dissemination from a sequestered infection site. MATERIAL AND METHODS: BALB/c mice were subcutaneously infected with P. gingivalis via use of a mouse chamber model. Tissue fluids from various sites were collected and cultured to determine the presence of P. gingivalis. Evans Blue dye was used to measure the dissemination ability of P. gingivalis. Kinin-associated molecules were introduced into mice, and their effects on bacterial dissemination and mouse pathology were monitored. RESULTS: P. gingivalis strain A7436 caused remote lesions and septicemia with severe cachexia, resulting in animal death. Intrachamber challenge with A7436 resulted in vascular permeability enhancement (VPE), as measured by the systemic infiltration of Evans Blue dye into chamber fluids. VPE was blocked by kininase and kinin receptor antagonist and enhanced by exogenous bradykinin and kininase inhibitor. Live bacteria were recovered from the subcutaneous perichamber and abdominal spaces (spreading), and from the blood (disseminating) of infected mice. Both kininase and kinin receptor antagonist reduced animal mortality as a result of infection with strain A7436 and decreased the number of bacteria recoverable from the blood, but they were not associated with bacterial spreading. CONCLUSIONS: The results suggest that activation of the kinin system is involved in the breach of the vascular barrier that permits dissemination of P. gingivalis.

Lethal outcome caused by Porphyromonas gingivalis A7436 in a mouse chamber model is associated with elevated titers of host serum interferon-gamma.

BACKGROUND/AIMS: Septic shock caused by gram-negative bacteria has been associated with cytokines produced by hosts. Porphyromonas gingivalis A7436, a disseminating strain, caused septic shock-like symptoms and even animal death in a mouse chamber model. However, P. gingivalis exhibits lower endotoxin activities in its lipopolysaccharide than other typical gram-negative bacteria. In this study, we examined the effects of P. gingivalis lethal infection on host pro-inflammatory cytokines production. METHODS: Nude and normal BALB/c mice were infected with a lethal dose of P. gingivalis A7436 using a mouse chamber model. Serum levels of tumor necrosis factor, interleukin (IL)-1beta, IL-12 and interferon-gamma were evaluated. The effects of tumor necrosis factor inhibitor (thalidomide) and anti-interferon-gamma antibody on infection outcomes were examined. RESULTS: All nude mice survived infectious challenge, whereas 100% of normal mice died with abdominal lesions. Bacterial cultures indicated P. gingivalis dissemination to the circulation. Serum levels of tumor necrosis factor, IL-1beta and IL-12 showed no significant differences between nude and normal mice. Thalidomide treatment did not protect normal mice from death but decreased remote lesion occurrence, with concurrent reduced bacterial counts recoverable from blood. There was a 3.5-fold elevation in normal mice serum interferon-gamma titers compared to those of nude mice and anti-interferon-gamma antibody treatment resulted in 100% protection from lethal outcome. CONCLUSION: Lethal outcome following P. gingivalis A7436 infection is T-lymphocyte dependent and involves an increase in systemic interferon-gamma levels. The data further indicate that P. gingivalis transvascular dissemination (bacteremia) alone is not sufficient for lethal outcome.

Oligonucleotide microarray for HLA-DRB1 genotyping: preparation and clinical evaluation.

In this study, HLA-DRB1 gene was genotyped by using the microarray technique. Oligonucleotide probes were designed based on partial sequences of various genotypes of HLA-DRB1, and were fixed on a silylated slide to form a microarray. The second exon of HLA-DRB1 gene in the extracted genomic DNA samples was amplified and labelled by means of polymerase chain reaction (PCR); then it was hybridized to the microarray. The microarray was scanned, and the result was analysed in order to determine the genotypes of HLA-DRB1 of the tested sample. A total of 1574 of 1592 clinical samples had accordant results of genotypes in either microarray assay or PCR-SSP assay; 8 of 10 samples that had inconsistent results of genotypes were proved to be microarray-assay reliable by confirmation of DNA sequencing. It is concluded that microarray is an alternative reliable method for HLA-DRB1 genotyping.

Genetic distances revealed by morphological characters, isozymes, proteins and RAPD markers and their relationships with hybrid performance in oilseed rape (Brassica napus L.).

Genetic distances (GDs) based on morphological characters, isozymes and storage proteins, and random amplified polymorphic DNAs (RAPD) were used to predict the performance and heterosis of crosses in oilseed rape (Brassica napus L.). Six male-sterile lines carrying the widely used Shaan2A cytoplasm were crossed with five restorer lines to produce 30 F1 hybrids. These 30 hybrids and their parents were evaluated for seven agronomically important traits and their mid-parent heterosis (MPH) at Yangling, Shaanxi province in Northwest China for 2 years. Genetic similarity among the parents based on 34 isozyme and seven protein markers was higher than that based on 136 RAPDs and/or 48 morphological markers. No significant correlation was detected among these three sets of data. Associations between the different estimates of GDs and F1 performance for some agronomic traits were significant, but not for seed yield. In order to enhance the predicting efficiency, we selected 114 significant markers and 43 favoring markers following statistical comparison of the mean values of the yield components between the heterozygous group (where the marker is present only in one parent of each hybrid) and the homozygous group (where the marker is either present or absent in both parents of each hybrid) of the 30 hybrids. Parental GD based on total polymorphic markers (GDtotal, indicating general heterozygosity), significant markers (GDsign, indicating specific heterozygosity) and favoring markers (GDfavor, indicating favoring-marker heterozygosity) were calculated. The correlation between GDfavor or GDsign and hybrid performance was higher than the correlation between GDtotal and hybrid performance. GDsign and GDfavor significantly correlated with plant height, seeds per silique and seed yield, but not with the MPH of the other six agronomic traits with the exception of plant height. The information obtained in this study on the genetic diversity of the parental lines does not appear to be reliable for predicting F1 yield and heterosis.

TNF-alpha polymorphisms and type 2 diabetes mellitus in Taiwanese patients.

Type 2 diabetic mellitus (type 2 DM) comprises more than 95% of all Taiwanese patients with DM. Tumor necrosis factor-alpha (TNF-alpha) expression is linked with insulin resistance, and is under strong genetic control. The correlation between TNF promoter genotypes and type 2 DM is still controversial, because discrepancies among different studies exist. Ethnic differences play certain roles in these conflicting results, because the distribution of TNF promoter polymorphisms is different among study subjects with different racial origins. Therefore, we examined the relationship between the incidence of type 2 diabetes in Taiwanese and two polymorphisms of the TNF-alpha promoter region (positions -238 and -308) as well as the correlation between these polymorphisms and the patients' biochemical manifestations. Genomic DNA was extracted from peripheral blood cells of 261 Taiwanese patients with type 2 DM and 189 non-diabetic control study subjects, and their TNF promoter G-238A and G-308A polymorphisms were analyzed by PCR-RFLP analysis. No significant association between TNF-alpha G-238A and G-308A polymorphisms with type 2 diabetic incidence was observed. However, associations between TNF-alpha G-238A and low-density lipoprotein-cholesterol and between G-308A promoter polymorphism and high-fasting plasma glucose levels, using multiple linear regression analysis with adjustment for the subjects' age, sex, body mass index and diabetic status, were found. Our results suggested that though TNF-alpha G-238A and G-308A polymorphisms were not involved in the pathogenesis of type 2 DM, type 2 diabetic patients carrying TNFA-A or TNF-308*2 genotype might be more susceptible to diabetic complications such as atherosclerosis.

Waste incineration and pulmonary function: an epidemiologic study of six communities.

This study investigated the chronic effects of emissions from three different waste incinerators on pulmonary function of both healthy and sensitive subjects with chronic respiratory symptoms. Participants were 8-80 years old, not currently smoking, and living in one of three communities each with an incinerator or one of three matched comparison communities. In total, 1018 subjects underwent a spirometric test once a year during 1992-1994. Exposure was assessed by three methods: living in an incinerator community; distance from the incinerator; and an incinerator exposure index, a function of the distance and direction of each subject's residence to the incinerator, days downwind, and average time spent outdoors. The results generally showed no statistically significant association between pulmonary function and these three incinerators, adjustment for gas oven/range use at home, length of residency, and smoking history in the mixed linear models. Two significant associations were that exposure to the hazardous waste incinerator in 1994 and to the municipal waste incinerator in 1993 were related to poor forced vital capacity. Sensitive subjects were not more adversely affected by incineration emissions than were hay fever or normal subjects. Possible explanations for the negative findings are low exposure levels and bias due to nondifferential misclassification of exposures.

Health effects of waste incineration: a review of epidemiologic studies.

There is an increasing trend toward using incineration to solve the problem of waste management; thus, there are concerns about the potential health impact of waste incineration. A critical review of epidemiologic studies will enhance understanding of the potential health effects of waste incineration and will provide important information regarding what needs to be investigated further. This study reviews the epidemiologic research on the potential health impact of waste incineration. Previous studies are discussed and presented according to their study population, incinerator workers or community residents, and health end points. Several studies showed significant associations between waste incineration and lower male-to-female ratio, twinning, lung cancer, laryngeal cancer, ischemic heart disease, urinary mutagens and promutagens, or blood levels of certain organic compounds and heavy metals. Other studies found no significant effects on respiratory symptoms, pulmonary function, twinning, cleft lip and palate, lung cancer, laryngeal cancer, or esophageal cancer. In conclusion, these epidemiologic studies consistently observed higher body levels of some organic chemicals and heavy metals, and no effects on respiratory symptoms or pulmonary function. The findings for cancer and reproductive outcomes were inconsistent. More hypothesis-testing epidemiologic studies are needed to investigate the potential health effects of waste incineration on incinerator workers and community residents.

Voltammetric studies of the effect of Cisplatin-liposome on Hela cells.

In this paper, the voltammetric method was used for the first time to study the effect of Cisplatin-liposome on Hela cells. The results showed the voltammetric behavior of Hela cells was irreversible and the peak current had linear relationship with the cell number. With both Cisplatin-liposome concentration and treating time increasing, the peak current decreased. The peak current decreasing was in accordance with the nuclear damage and loss of mitochondrial membrane potential revealed by two-photon laser scanning microscopy and confocal laser scanning microscopy. This voltammetric method may provide a simple way to study the electron-transfer mechanism in drug-treating cells.

The ubiquitin-activating enzyme E1-like protein in lung cancer cell lines.

The UBE1L gene isolated from the chromosome 3p21 region has an extremely reduced level of mRNA in lung cancer. Sequence analysis showed a 45% homology to the human ubiquitin-activating enzyme E1 at the amino acid level. To further characterize the protein product, we generated UBE1L protein-specific antibodies. Immunoblot analysis revealed a full-length gene product of approximately 112 kDa. Assessment of the level and distribution pattern of the UBE1L protein in normal and tumor tissue using the generated antibodies showed that the UBE1L protein was present in normal lung cells and non-lung cancer cell lines, but was undetectable in all 14 human lung cancer cell lines analyzed. This difference in expression of the UBE1L protein between normal lung tissue and lung tumor-derived cell lines suggests a possible involvement of an E1-like protein in the origin and/or progression of lung tumors.

Does arsenic exposure increase the risk for circulatory disease?

Studies of residents in communities with high endemic concentrations of arsenic in drinking water suggest a deleterious effect on the circulatory system; however, studies among workers with high occupational exposures generally have shown either no or weak associations. This discrepancy could be a result of the healthy worker effect, including the healthy hire component and the healthy worker survivor effect (HWSE). Therefore, the authors conducted analyses of arsenic exposure in relation to circulatory disease mortality among 2,802 Tacoma, Washington, smelter workers by using 1) internal comparisons to control for the healthy hire effect and 2) the lagging method, adjustment for employment status, and the G-null test to control for the HWSE. Both lagging and adjustment for work status increased circulatory mortality rate ratios at all exposure levels, as compared with a baseline Poisson model. This excess mortality was limited to cardiovascular disease; no excess was observed for cerebrovascular disease. G-null analyses suggested no adverse effect, but power was very limited for this analysis. Overall, these results may indicate that the HWSE obscures an effect of arsenic on circulatory disease. Since cardiovascular deaths constitute about one-third of total mortality, small rate ratios translate into large numbers of excess deaths and, if causal, could be of wide public health significance. Further studies of arsenic exposure and cardiovascular disease are needed, and those conducted in occupational cohorts must control for the HWSE.

[Relation of pilots symptoms with some physiological parameters under vestibular stimulus].

OBJECTIVE: To investigate the relation of vestibular stimulus induced symptoms to electrogastrogram (EGG), electronystagmogram (ENG), acupoint potential (AP), skin temperature (ST) heart rate variability (HRV) and content of urine hormones. METHOD: The physiological parameters were recorded before, during and after vestibular stimuli. Graybiel's scoring standard was used, and progressive regression analysis of symptoms and physiological parameters were made. RESULT: The regression equations were obtained from data before, during and after the stimuli. CONCLUSION: Three regression equations might be used.

When to be skeptical of negative studies: pitfalls in evaluating occupational risks using population-based case-control studies.

This study investigated arsenic and lung cancer incidence in a community setting in the Montreal area. Job histories and sociodemographic factors were collected by interview from 857 lung cancer cases, 533 general population controls, and 1,360 controls with other cancers. Chemist-hygienists assessed each subject's life-time occupational exposure to 294 substances. Logistic regressions yielded arsenic/lung cancer odds ratios of 1.1 (95% confidence interval = 0.60, 1.7) based on cancer controls, and 0.82 (95% confidence interval = 0.41, 1.6) based on population controls. Risk did not rise with increasing level or probability of exposure. Worksite studies consistently show lung carcinogenicity from arsenic. Since confounding from other chemicals was well controlled, the most likely explanation is substantially lower exposures than in previous studies. The lack of association in this study demonstrates the need for caution in interpreting negative findings from population-based case-control studies, particularly when exposures are low or rare, as well as the difficulty in generating hypotheses from such studies.

Contribution of cadmium in cigarettes to lung cancer: an evaluation of risk assessment methodologies.

This investigation concerned the use of quantitative risk assessment for estimating cancer mortality at low-level exposures. We empirically tested whether extrapolating by linear no-threshold models predicted implausible risks at low-level exposures. Cadmium in cigarette smoke was the low-level exposure, and extrapolation was based on potencies estimated from an occupational study and a rodent cancer bioassay. Inhaled cadmium in mainstream and sidestream smoke was estimated from published laboratory experiments. Smoking-specific lung cancer and all-cause mortality rates were estimated from large population-based studies. The mortality rates, amount of inhaled cadmium, and potency values were used to construct life tables for calculating lifetime lung cancer risk with and without a contribution from cadmium in cigarette smoke. The epidemiologic data predicted that 1 to 18 lung cancer deaths per 10,000 smokers may be attributable to inhaled cadmium in cigarette smoke, or approximately 0.2% to 1.6% of smoking-induced lung cancer deaths. Upper 95% bounds on these figures are 7 to 95 lung cancer deaths or 1.6% to 8.8% of smoking-related deaths. The rodent data predicted that 80 to 416 lung cancer deaths per 10,000 smokers (95% upper bounds: 136-707) or 13% to 47% (23-81%) of smoking-induced lung cancer mortality may be attributable to cadmium in cigarette smoke. Linear extrapolation from human data appears to provide plausible estimates of risk at low doses. Considering the large number of carcinogens present in cigarette smoke, the extrapolation from rodents appears to overestimate human risks.(ABSTRACT TRUNCATED AT 250 WORDS)