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The aims of this study were to explore the frequency of somatic symptom disorder (SSD) and the relationship between SSD and somatic, psychological, and social factors in Chinese patients with breast cancer.This multicenter cross-sectional study enrolled 264 patients with breast cancer from three different departments in Beijing. The structured clinical interview for fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (SCID-5) for SSD. Standardized questionnaires and clinical data were used to compare patients with and without SSD.Somatic symptom disorder was diagnosed in 21.6% (57/264) of all enrolled patients. No differences were found between SSD patients and non-SSD patients in terms of sociodemographic characteristics and tumor-specific variables, except radiotherapy. However, patients with SSD reported higher levels of depression, anxiety and cancer-related worry. They also showed a longer duration of symptoms, greater impairment in daily life, more concern over their physical complaints and more doctor visits. In a stepwise binary logistic regression analysis, among others, higher health anxiety (WI-8, Exp(B) = 0.107, p = 0.009) and more doctor visits (OR = -1.841, p 0.001) showed a significant association with SSD; the model explained 53.7% of the variance.Similar to other physical diseases, there is a high prevalence of SSD in patients with breast cancer. Somatic symptom disorder patients differ from non-SSD patients by exhibiting higher cancer-related emotional distress and dysfunctional illness perception and behavior. There remain substantial challenges in the diagnosis of SSD in patients with cancer and other medical conditions.ChiCTR2100051525.

OBJECTIVE We aim to explore the capacity of perioperative pupillary variables to predict acute pain in the post-anesthesia care unit (PACU). METHODS Patients scheduled to undergo thoracic or abdominal surgery under general anesthesia between April 2021 and June 2021 were enrolled. We measured the pupil diameter, pupillary light reflex (PLR), and pupillary reflex dilatation 5 min before anesthesia induction (T1), 5 min after intubation (T2), at the end of anesthesia (T3), immediately before extubation (T4), and 5 min after extubation (T5). We assessed the early postoperative pain intensity in the PACU using Numeric Rating Scales (NRS) at recovery, 5 min after recovery, and 10 min after recovery. Logistic regression models were used to evaluate the association between perioperative pupillary variables and postoperative pain intensity. RESULTS Fifty-one patients were enrolled, 50 of whom were included in the final analysis. A total of 13 patients (26%) needed remedial analgesia in the PACU. Pupil parameters at T1, T2, T3, and T5 were not associated with NRS in the PACU. Multiple logistic regression models and receiver operating characteristic (ROC) curves indicated that only latency of PLR at T4 can predict postoperative acute pain. The ROC analysis showed that the cutoff value for latency of PLR at T4 was 0.29 s to discriminate between no pain and pain, and the area under the curve was 0.778 (95% CI 0.634-0.922, p = 0.002) with sensitivity 50.0% and specificity 91.7%. CONCLUSION The latency of PLR immediately before extubation may be a useful predictor for postoperative acute pain in the PACU.

To facilitate the extraction of source image information, and preserve the consistency of heterogeneous regional features, a multiscale image fusion method based on a joint cascaded convolutional coding network (JCa2Co) is proposed. The JCa2Co network can retain vast quantities of information from source images in a multiscale perspective. The approach includes an encoder, a fusion layer and decoder. In the fusion layer, the Fuzzy Regional Characteristics (FRC) scheme is considered, and the multiscale feature maps are extracted from image subregions to ensure regional image consistency. Firstly, a joint cascaded encoder is used to extract multiscale features of the source image, in which the output of each layer is connected to every other layer. The fusion layer based on FRC is then performed to fuse each scale feature. Finally, the fused image is reconstructed by the decoder. In addition, to verify the regional consistency of the fused image, a regional consistency measure is proposed. Experiments are performed on the TNO Image Fusion Database. The experimental results exhibit that the proposed JCa2Co method has better comprehensive performance than the eight state‐of‐the‐art fusion methods. Moreover, it can effectively integrate meaningful information in infrared and visible images and has excellent performance in objective evaluation and visual quality, which is beneficial to target recognition and tracking.

BACKGROUND This study aims to compare the burnout level and perceptions of burnout between oncology physicians and nurses, and to explore the relationship between these perceptions and the burnout level in physicians and nurses separately. METHODS The whole crew of the Peking University Cancer Hospital was invited to participate in the survey. Maslach Burnout Scale Human Services Survey (MBI-HSS) was used. Ten additional items on the perceptions of burnout were added to assess concerns on burnout, perceptions on the negative impact of burnout and perceptions on how to prevent burnout. RESULTS In total, 862 (71%) oncology clinicians completed the questionnaire, including 285 physicians (33%) and 577 (67%) nurses. The proportion of the high risk of low personal accomplishment (PA) is higher in nurses than in physicians (39.3% V.S. 29.8%, p = 0.007). Most clinicians (72.2% of physicians, 82.4% of nurses) would like to participant in interventions to prevent burnout, but only a few of them (5.7% of physicians, 4.1% of nurses) had an opportunity to participate in. Both physicians (91.9%) and nurses (89.8%) rated increasing paid vacation as the most priority strategy to prevent burnout. The job-hopping intention is correlated to a high level of burnout in both physicians and nurses. CONCLUSIONS The burnout level did not differ significantly between oncology nurses and physicians, except the low PA level. There was a big gap between their needs for burnout interventions and the resources they really had. The clinicians with a job-hopping intention should be paid attention to their burnout.

OBJECTIVE To assess changes in body image distress (BID) over time, identify factors associated with BID, and explore the mediating role of body image on the longitudinal association between stoma status (permanent stoma, temporary stoma, or nonstoma) and psychological distress in postoperative colorectal cancer (CRC) patients in China. METHODS Participants (N = 255) 1-2 weeks postsurgery completed self-report questionnaires assessing BID (Body Image Scale) and psychosocial distress (Distress Thermometer, Hospital Anxiety and Depression Scale); 212 (83%) completed 6-month follow-up surveys. Generalized estimating equations were used to identify factors associated with BID for longitudinal data analysis. RESULTS A total of 46.7% of participants reported BID at follow-up. Prevalence of BID and BID scores did not significantly change over time in the total sample. Body image scores decreased in patients whose temporary stoma was removed during follow-up (p

BACKGROUND Both demoralization and depression are common forms of psychological distress in cancer patients. This study aimed to investigate the severity of demoralization in Chinese cancer patients and to explore the factors influencing depression and demoralization and their effects on quality of life to better understand the differences and the relationship between demoralization and depression. METHODS Cross-sectional study design, in-patients sequentially recruited from a tertiary-level cancer hospital in Beijing between January 2016 and April 2016 completed Mandarin version of Demoralization Scale (DS-MV), Patient Health Questionnaire-9 (PHQ-9), Revised Life Orientation Test (CLOT-R), Beck Hopelessness Scale (BHS), and the 12-items Short Form Health Survey, version 2 (SF-12 V2) and provided socio-demographic and clinical information. RESULTS 296/424 (70.0%) of patients completed questionnaires. The mean score of DS is 30.4 (SD = 13.0). There are 28% (83/296) patients who experienced a low level of depression but a high level of demoralization. Resignation medical coping method (b = 0.279, P < .001), hopelessness (b = 0.492, P < .001), positive life orientation (b = -0.170, P < .001), and education level (b = -0.132, P < .001) were found to be predictors of demoralization, while only resignation medical coping method (b = 0.373, P < .001) and hopelessness (b = 0.350, P < .001) were found to be predictors of depression. Depression is a mediator between demoralization and physical aspects of quality of life (γ = -0.1604, LLCI = -0.244, ULCI = -0.080). CONCLUSION Demoralization is a prevalent psychiatric problem in Chinese cancer patients, and a large proportion of patients had low depression but high demoralization. Therefore, screening for demoralization in Chinese oncology practice is essential. A positive life orientation was found to be protective against demoralization.

Background Pretibial dystrophic epidermolysis bullosa (DEB-Pt) is an extremely rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by blistering and scar formation. The pathogenesis of the disease is mainly due to the mutation of COL7A1 gene encoding type VII collagen fibers, resulting in the destruction of the anchoring structure of the epidermis and dermis. Aims The purpose of this study was to discover the major mutations in DEB-Pt by studying this family and reviewing the literature on DEB-Pt. Patients/methods We examined the patients by clinical manifestations and histopathology, extracted DNA from blood samples from 7 individuals in the family via FlexiGene DNA Kit, and then sequenced the samples using whole-exon sequencing (WES). Result Characteristic clinical manifestations such as blisters and scars were found in the patients. Genetic analysis revealed a missense mutation in exon 87(c.6860G>A) of COL7A1 gene, which has never been reported before. Conclusion The discovery of the new mutation extends the COL7A1 mutation database. We also reviewed all the mutation in DEB-Pt from relevant literature at home and abroad. This will facilitate the molecular diagnosis, treatment, and prognosis of DEB-Pt.

Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non‐BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients (P

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease characterized by hamartomas in multiple organ systems. This study was performed in one familial and two sporadic cases with TSC. Two novel mutations (c.1884_1887delAAAG and c.5266A>G) and two previously reported mutations (c.4258_4261delTCAG and c.1960G>C) were identified by direct DNA sequencing. Of the four mutations, c.1884_1887delAAAG and c.1960G>C were found in a family and identified in the same allele by TA cloning sequencing. However, c.1960G>C was reported to be non-pathogenic. Furthermore, correlations between genotypes and phenotypes of Chinese Han patients since 2014 were performed by paired χ2 -tests in our published work review, which has not been reported. The results showed that patients with TSC2 mutations had a higher frequency of mental retardation and there were no significant differences of seizures and skin lesions with TSC1 mutations. Genetically, they had a higher frequency of familial inheritance.

This work evaluates chronic safety in middle-aged ovariectomized rats supplemented with different dosages of green tea polyphenols (GTP) in drinking water. The experiment used 6-mo-old sham (n = 39) and ovariectomized (OVX, n = 143) female rats. All sham (n = 39) and 39 of the OVX animals received no GTP treatment and their samples were collected for outcome measures at baseline, 3 mo, and 6 mo (n = 13 per group for each). The remaining OVX animals were randomized into 4 groups receiving 0.15%, 0.5%, 1%, and 1.5% (n = 26 for each) of GTP (wt/vol), respectively, in drinking water for 3 and 6 mo. No mortality or abnormal treatment-related findings in clinical observations or ophthalmologic examinations were noted. No treatment-related macroscopic or microscopic findings were noted for animals administered 1.5% GTP supplementation. Throughout the study, there was no difference in the body weight among all OVX groups. In all OVX groups, feed intake and water consumption significantly decreased with GTP dose throughout the study period. At 6 mo, GTP intake did not affect hematology, clinical chemistry, and urinalysis, except for phosphorus and blood urea nitrogen (increased), total cholesterol, lactate dehydrogenase, and urine pH (decreased). This study reveals that the no-observed-adverse-effect level (NOAEL) of GTP is 1.5% (wt/vol) in drinking water, the highest dose used in this study.

Purpose This study compared self-reported burnout between dual-role oncologists (oncologists who also do psychosocial work) and single-role oncologists, to explore if dual role is protective against or a risk factor for burnout. Methods Dual-role oncologists from across China (n = 131) were consecutively recruited via the Chinese Psychosocial Oncology Society and asked to identify single-role oncologist peers (n = 168) working in the same institution. Participants completed an anonymous online questionnaire, which included measures of demographic and work characteristics, Maslach Burnout Inventory–Human Services Survey, the Short Version Effort-Reward Inventory, the Job Demands-Resources (JD-R) Scales, and Work and Meaning Inventory. Fully adjusted multivariate analyses compared burnout scores for the 2 groups. Results Group analysis revealed single-role participants' scores indicated significantly poorer performance than dual-role participants for depersonalization (DP), work-family conflict (JD-R demands scale), and decision authority (JD-R scale). Single-role participants showed an increased risk of DP. Higher effort-reward imbalance ratio predicted greater DP in single-, dual-role and pooled participants, and emotional exhaustion (EE) in pooled- and dual-role participants. Overcommitment was independently associated with EE in all 3 groupings, with JD-R scores among pooled- and dual-role groups, while higher decision authority scores were associated with decreased EE. Work and Meaning Inventory was associated with a decreased risk of DP among pooled and dual-role participants. Conclusion Differences in burnout-related DP scores between dual- and single-role oncologists are consistent with a protective effect from a psychosocial orientation in oncologists.

Objective: We researched associations between somatic symptom severity (SSS), and physical and psychological factors in Chinese breast cancer patients. Methods: This multicenter cross-sectional study enrolled 255 Chinese breast cancer patients of different stages and treatment phases. They answered standard instruments assessing SSS (Patient Health Questionnaire [PHQ]-15), depression (PHQ-9), anxiety (General Anxiety Disorder [GAD]-7), health anxiety (Whiteley-7 [WI-7]), illness perception (Brief-Illness Perception Questionnaire [IPQ]), illness attribution (Illness Perception Questionnaire-Revised [IPQ-R]), and sense of coherence (Sense of Coherence [SOC]-9). Logistic regression was applied to identify the strongest correlates with SSS. Results: Our sample of high (PHQ-15 ≥ 10) and low SSS differed significantly in the following physical and psychological variables: symptom duration (r = 0.339, P

Simulations at multiple levels were performed to investigate the aqueous adsorption of phthalate esters (PAEs) on carbon nanoparticles and to find the competitive effect of a low molecular weight natural organic acid (benzoic acid) on the adsorption process. Six PAEs of varying alkyl side chain lengths and three carbon-based nanomaterials including a single-walled carbon nanotube (SWNT), double-walled carbon nanotube (DWNT), and graphene (G) were studied. Results showed that the adsorption energies calculated using density functional theory increase with increasing length of the PAE alkyl chain. G exhibits higher adsorption capacity for the PAEs than SWNT and DWNT. The absolute adsorption energies of these systems also display a positive linear correlation with the hydrophobicity of the PAE molecules. Molecular dynamics simulations indicate that the presence of neutral/anionic benzoic acid in water alleviates the PAE adsorption. Furthermore, anionic benzoic acid exerts more impact on the PAE adsorption than the neutral form.

Understanding how the detailed nanoscale structure governs the interfacial interactions and reactivities is key to the exploration of nanostructured chemical sensors. We describe herein novel findings of an investigation of a palladium-gold alloy nanowire interface for hydrogen sensing. A dielectrophoretic growth pathway was utilized for controllable fabrication of the alloyed nanowires with minimum branching structures on a microelectrode device using controlled ratios of palladium and gold precursors in a two-step mechanism, a nucleation process initiated at a lower alternating current (AC) frequency followed by a growth process at a higher frequency up to 15 MHz. The nanowires showed a reduced branching propensity and highly oriented 1D feature, with the bimetallic composition scaling linearly with the frequency. The nanowires exhibited excellent responses to hydrogen in concentrations as low as 0.5 % by volume. The hydrogen-response characteristic represents an optimized balance of the gold-induced lattice expansion of palladium and hydrogen adsorption-induced phase and stress changes, a new insight into the sensing mechanism of the alloy nanowire. The mechanistic sensing details are also discussed in correlation with the growth mechanism, which provides a new insight into the synergy of the bimetallic composition of the alloy nanowires for the enhanced sensitivity for the detection of hydrogen.

Objective Patients with breast cancer are able to gain psychological benefits from cancer diagnosis and treatment, such as a greater purpose of life and closer relationships, termed as ‘benefit finding’ (BF). The objective of this study was to determine the effects of sociodemographic, pathological, and psychological variables on BF in women with non-metastatic breast cancer. Methods A total of 404 patients with breast cancer were recruited to complete a demographic survey, a Chinese version of the Benefit Finding Scale, the Optimism-pessimism Scale, the Multidimensional Scale of Perceived Social Support, and the Cognitive Emotion Regulation Questionnaire during the first week after the confirmation of the diagnosis (T1). All participants finished the Chinese version of the Benefit Finding Scale again 6 weeks after diagnosis (T2). Results Age and education of patients, perceived social support from family, acceptance, positive reappraisal, and the baseline level of BF exhibited a positive prediction on BF. Education, pessimism, and perceived social support from family had a positive prediction and perceived social support from friends and refocus on planning had a negative prediction on the family relationship of BF. Education, perceived social support from family and friends, and the baseline level of BF had a positive prediction on the acceptance of BF. Conclusions Perceived social support and cognitive emotion regulation strategies employed in response to breast cancer are important contributing factors to BF in women with breast cancer. In order to improve the longer-term adaptation of patients, benefit finding, either directly or via cognitive emotion regulation strategies, could be targeted for intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Increased use and production of carbon nanomaterials (e.g., fullerene C60) and ionic liquids (ILs) may result in their concomitant releases into the environment. Inevitably there will be interactions between carbon nanoparticles (CNPs) and ILs. However, experimental data on the interaction of CNPs with ILs are not readily available, and the mechanism behind the interactions is still elusive. To contribute to an understanding of the molecular interactions established between CNPs and ILs, theoretical investigations at multiple levels were performed to determine the interactions of C60 with 6 different imidazolium-based ILs. The results indicate that C60 mainly interacts with the IL molecules through the van der Waals, π–cation, and hydrophobic interactions. Mulliken population analysis suggests that charge transfer occurs from the IL to C60 during the C60–IL interaction. The self-diffusion coefficient (D) of C60 in [C60 + IL] systems reaches the maximum in the case of moderate C60–IL interaction (interaction energy, EINT), implying that in this case a good dispersion of an agglomerate species of C60 is obtained. The D value of C60 in [C60 + IL + water] systems increases with an increase of the EINT, implying that the presence of ILs can play an important role in the aqueous dispersion of the C60 agglomerate. Environ Toxicol Chem 2014;33:1802–1808. © 2014 SETAC

Aflatoxins (AFs) and fumonisins (FBs) can co-contaminate foodstuffs and have been associated with hepatocellular and esophageal carcinomas in humans at high risk for exposure. One strategy to reduce exposure (and toxicity) from contaminated foodstuffs is the dietary inclusion of a montmorillonite clay (UPSN) that binds AFs and FBs in the gastrointestinal tract. In this study, the binding capacity of UPSN was evaluated for AFB1, FB1 and a combination thereof in Fischer 344 rats. Rats were pre-treated with different dietary levels of UPSN (0.25% or 2%) for 1 week. Rats were gavaged with a single dose of either 0.125 mg AFB1 or 25 mg FB1 per kg body weight and a combination thereof in the presence and absence of an aqueous solution of UPSN. The kinetics of mycotoxin excretion were monitored by analyzing serum AFB1 -albumin, urinary AF (AFM1) and FB1 biomarkers over a period of 72 h. UPSN decreased AFM1 excretion by 88-97%, indicating highly effective binding. FB1 excretion was reduced, to a lesser extent, ranging from 45% to 85%. When in combination, both AFB1 and FB1 binding occurred, but capacity was decreased by almost half. In the absence of UPSN, the combined AFB1 and FB1 treatment decreased the urinary biomarkers by 67% and 45% respectively, but increased levels of AFB1 -albumin, presumably by modulating its cytochrome metabolism. UPSN significantly reduced bioavailability of both AFB1 and FB1 when in combination; suggesting that it can be utilized to reduce levels below their respective thresholds for affecting adverse biological effects.

Background This study aimed to explore the relationship between cancer-related fatigue (CRF) and personality in patients with breast cancer after chemotherapy. Methods A cross-sectional study was conducted to study the relationship between CRF and personality in breast cancer patients after chemotherapy. CRF and personality were measured by the cancer fatigue score and the Eysenck Personality Questionnaire, respectively. Results A total of 300 breast cancer patients who had received chemotherapy were recruited to this study. Eysenck Personality Questionnaire scores of psychoticism, introversion, and extroversion in the patients were lower than the norm level (p

Aflatoxin B1 (AFB1) is immunotoxic to animals and a suspected immunosuppressant in humans. In this study, we investigated the effects of AFB1 on splenic lymphocyte phenotypes and the inflammatory cytokine expression in male F344 rats. Exposure of animals to AFB1 [5-75 µg kg(-1) body weight (BW)] for 1 week showed dose-dependent decreases in the percentage of splenic CD8(+) T cells and CD3(-) CD8a(+) NK cells. A general inhibition of the expression of interleukin (IL)-4 and interferon (IFN)-γ by CD4(+) T cells, IL-4 and IFN-γ by CD8a(+) cells, and tumor necrosis factor (TNF)-α expression by natural killer (NK) cells was also found; however, no concurrent histological changes in spleen tissue were present, suggesting acute immunosuppression without overt toxicity. Five-week exposure with AFB1 significantly increased the percentages of CD3(+) and CD8(+) T cells, especially at low doses (≤ 25 µg kg(-1)). AFB1 treatment significantly decreased the anti-inflammatory cytokine IL-4 expression by CD4(+) T cells and significantly increased the pro-inflammatory cytokine IFN-γ expression by CD4(+) T cells and TNF-α expression by NK cells. These results indicated that repeated AFB1 exposure promotes inflammatory responses by regulating cytokine expression. Our data provides novel insights into the mechanisms by which AFB1 exposure differentially modulates the cell-mediated immune responses and suggests the involvement of an inflammatory response upon repeated exposure.

Pancreatic cancer is a devastating malignancy, characterized by intrinsic or acquired resistance to conventional chemotherapies. Recent evidences suggest an involvement of tyrosine kinase pathway in the regulation of multidrug resistance (MDR) protein gene expression. The aim of this study was to test whether gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor could regulate the MDR protein gene expression and sensitize the resistant cancer cells to chemotherapy. The gene expression of MDR proteins (MRP1, MRP2, MRP3, and PGP) were evaluated by quantitative RT-PCR, and expression levels of various tyrosine kinases were investigated by quantitative RT-PCR and Western blot in pancreatic cancer cell line. MTT assay was used for evaluating the effect of chemotherapeutic agents. Chemotherapeutics induced drug resistance by regulating the gene expression of MDR proteins (MRP1, MRP2, and MRP3), and increased the gene expression of RAF1/ERK and the phosphorylation of ERK in pancreatic cancer Bxpc-3 cells. Gefitinib caused an inhibition of p-ERK tyrosine kinase activation in a dose-dependent manner, and reversed gemcitabine-induced RAF1/ERK gene expression and p-ERK activation. In addition, a reversal of MDR proteins gene expression was achieved by gefitinib, which sensitized resistant cells to gemcitabine. This study demonstrated that MDR of Bxpc-3 cell is involved in the RAF1/ERK tyrosine kinase pathway. Gefitinib reverses the MDR protein gene expression and restores sensitivity of resistant cells to gemcitabine via RAF1/ERK signaling pathway. Combination of gefitinib with conventional chemotherapeutic agents may offer a new approach for the treatment of patients with pancreatic cancer.

Aflatoxin B1 (AFB1) and T-2 toxin (T-2) are important food-borne mycotoxins that have been implicated in human health and as potential biochemical weapons threats. In this study the acute and combinative toxicity of AFB1 and T-2 were tested in F-344 rats, mosquitofish (Gambusia affinis), immortalized human hepatoma cells (HepG2) and human bronchial epithelial cells (BEAS-2B). Preliminary experiments were conducted in order to assess the acute toxicity and to obtain LD50, LC50 and IC50 values for individual toxins in each model, respectively. This was followed by testing combinations of AFB1 and T-2 to obtain LD50, LC50 and IC50 values for the combination in each model. All models demonstrated a significant dose response in the observed parameters to treatment. The potency of the mixture was gauged through the determination of the interaction index metric. The results of this study demonstrate that these two toxins interacted to produce alterations in the toxic responses generally classifiable as additive; however, a synergistic interaction was noted in the case of BEAS-2B. It can be gathered that this combination may pose a significant threat to public health and further research needs to be completed addressing alterations in metabolism and detoxification that may influence the toxic manifestations in combination. Copyright © 2005 John Wiley & Sons, Ltd.

The worldwide human exposure to aflatoxin B1 (AFB1), particularly in developing countries, remains to be a serious public health concern. Although AFB1 is best known as a hepatocarcinogen, epidemiological studies have shown a positive association between human lung cancer occurrence and inhalation exposure to AFB1. Cytochrome P450 (CYP)-catalyzed metabolic activation is required for AFB1 to exert its carcinogenicity. Previous studies have identified CYP1A2 and CYP3A4 as the major enzymes for AFB1 activation in human liver. However, the key CYP enzymes in human lung that can efficiently activate AFB1 in situ are unknown. In the present study, we demonstrate that CYP2A13, an enzyme predominantly expressed in human respiratory tract, has a significant activity in metabolizing AFB1 to its carcinogenic/toxic AFB1-8,9-epoxide and AFM1-8,9-epoxide at both low (15 microM) and high (150 microM) substrate concentrations. Under the same conditions, there was no detectable AFB1 epoxide formation by CYP2A6, which was also reported to be involved in the metabolic activation of AFB1. Consistent with the activity data, there was an approximately 800-fold difference in LC50 values of AFB1 (48-hr treatment) between Chinese hamster ovary (CHO) cells expressing CYP2A13 and CYP2A6 (50 nM versus 39 microM). We further demonstrate that amino acid residues Ala117 and His372 in CYP2A13 protein are important for AFB1 epoxidation and its related cytotoxicity. Our results suggest that CYP2A13-catalyzed metabolic activation in situ may play a critical role in human lung carcinogenesis related to inhalation exposure to AFB1.