Cytochrome P450 2A13 mediates the neoplastic transformation of human bronchial epithelial cells at a low concentration of aflatoxin B1

Zhang, Zhan; Lu, Huiyuan; Huan, Fei; Cromie, Meghan; Yang, Xianhui; Wang, Yun; Wang, Xichen; Wang, Xinru; Wang, Shoulin

doi:10.1002/ijc.28489

Cited by 35 publications

(19 citation statements)

References 36 publications

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“…To date, the published literature on AFB1 airway exposure mainly focuses on its carcinogenic effects in the lungs (Donnelly et al, 1996a(Donnelly et al, , 1996bChen and Kensler, 2014;Zhang et al, 2014;Van Vleet et al, 2001), but very few studies have assessed the association between AFB1 inhalation and its effects on the serum AFB1 adduct level. Two epidemiological studies revealed animal-feed production workers' exposure to airborne AFB1, but only a portion of them had detectable levels of serum AFB1 (Autrup et al, 1991;Viegas et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

How does airway exposure of aflatoxin B1 affect serum albumin adduct concentrations? Evidence based on epidemiological study and animal experimentation

Lai

Yang

et al. 2014

J. Toxicol. Sci.

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-Aflatoxin B1 (AFB1) airway inhalation represents an additional route of exposure to this toxin. However, the association between AFB1 inhalation and serum AFB1 albumin adducts remains unclear. The aim of this study was to explore the association between airway exposure to AFB1 and serum AFB1 albumin adduct concentrations via an epidemiological study, as well as in an AFB1 airway exposure animal model. Our epidemiological study was conducted in a sugar factory in the Guangxi Autonomous Region of China. In order to examine fungal contamination, air samples were obtained in the workshop and areas outside the workshop, such as the office and nearby store. Dust samples were also collected from the bagasse warehouse and presser workshop, and were analyzed using an indirect competitive enzyme-linked immunosorbent assay (ELISA). Additionally, blood samples were collected from a total of 121 workshop workers, and a control group (n = 80) was comprised of workers who undertook administrative tasks or other work outside the workshop. The animal experiment was conducted in the laboratory animal center of Guangxi Medical University, where a total of 60 adult male rabbits were involved in this study. By intubation, AFB1 was administered in three groups of rabbits daily, at dose rates of 0.075, 0.05 and 0.025 mg/kg/day for a period of 7 days. Blood samples were collected on day 1, day 3, day 7 and day 21, and the measurements of the AFB1 albumin adducts in the serum were performed by a double antibody sandwich ELISA. The epidemiological study showed that serum albumin adducts were detected in 67 workshop workers (55.37%), and the values ranged 6.4 pg/mg albumin to 212 pg/mg albumin (mean value: 51 ± 4.62 pg/mg albumin). In contrast, serum albumin adducts were detected in only 7 control group participants, with the values ranging from 9 pg AFB1/mg albumin to 59 pg/mg albumin (mean value: 20 ± 13.72 pg/mg albumin). The animal experiment revealed that the rabbits had detectable levels of AFB1 in their serum with a minimum effective dose of 0.05 mg/kg/day; while 11 of 17 (64.71%) rabbits had detectable levels of AFB1 albumin adducts in the high exposure group (0.075 mg/kg/day), and only 5 rabbits (26.32%) had detectable levels of AFB1 albumin adducts in the moderate exposure group (0.05 mg/kg/day). No rabbits had detectable levels of AFB1 albumin adducts in the low exposure group (0.025 mg/kg/day). Our results demonstrated that only exposure to a certain level of AFB1 would result in detectable levels of serum AFB1 albumin adducts. Interventional programs aimed at reducing exposure to AFB1 by inhalation are urgently needed in high-risk populations. Additional large-sample, well-designed randomized controlled trials are needed to further confirm our results.

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Section: Discussionmentioning

confidence: 99%

How does airway exposure of aflatoxin B1 affect serum albumin adduct concentrations? Evidence based on epidemiological study and animal experimentation

Lai

Yang

et al. 2014

J. Toxicol. Sci.

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“…The immunohistochemistry and immunoblotting assays were as described in our previous study [39]. The expression of CD 3, CD77, F4/80 and P65 were determined by immunohistochemistry assay.…”

Section: Methodsmentioning

confidence: 99%

Caffeic acid ameliorates colitis in association with increasedAkkermansiapopulation in the gut microbiota of mice

et al. 2016

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Emerging evidence shows that dietary agents and phytochemicals contribute to the prevention and treatment of ulcerative colitis (UC). We first reported the effects of dietary caffeic acid (CaA) on murine experimental colitis and on fecal microbiota. Colitis was induced in C57BL/6 mice by administration of 2.5% dextran sulfate sodium (DSS). Mice were fed a control diet or diet with CaA (1 mM). Our results showed that dietary CaA exerted anti-inflammatory effects in DSS colitis mice. Moreover, CaA could significantly suppress the secretion of IL-6, TNFα, and IFNγ and the colonic infiltration of CD3+ T cells, CD177+ neutrophils and F4/80+ macrophages via inhibition of the activation of NF-κB signaling pathway. Analysis of fecal microbiota showed that CaA could restore the reduction of richness and inhibit the increase of the ratio of Firmicute to Bacteroidetes in DSS colitis mice. And CaA could dramatically increase the proportion of the mucin-degrading bacterium Akkermansia in DSS colitis mice. Thus, CaA could ameliorate colonic pathology and inflammation in DSS colitis mice, and it might be associated with a proportional increase in Akkermansia.

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“…The protein level of DHODH in tumor tissues was detected by immunohistochemistry assay according to previous study [51]. …”

Section: Methodsmentioning

confidence: 99%

Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells

Yang

Chen

et al. 2016

Oncotarget

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Celastrol, extracted from “Thunder of God Vine”, is a promising anti-cancer natural product. However, its effect on acute promyelocytic leukemia (APL) and underlying molecular mechanism are poorly understood. The purpose of this study was to explore its effect on APL and underlying mechanism based on metabolomics. Firstly, multiple assays indicated that celastrol could induce apoptosis of APL cells via p53-activated mitochondrial pathway. Secondly, unbiased metabolomics revealed that uridine was the most notable changed metabolite. Further study verified that uridine could reverse the apoptosis induced by celastrol. The decreased uridine was caused by suppressing the expression of gene encoding Dihydroorotate dehydrogenase, whose inhibitor could also induce apoptosis of APL cells. At last, mouse model confirmed that celastrol inhibited tumor growth through enhanced apoptosis. Celastrol could also decrease uridine and DHODH protein level in tumor tissues. Our in vivo study also indicated that celastrol had no systemic toxicity at pharmacological dose (2 mg/kg, i.p., 21 days). Altogether, our metabolomics study firstly reveals that uridine deficiency contributes to mitochondrial apoptosis induced by celastrol in APL cells. Celastrol shows great potential for the treatment of APL.

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Cytochrome P450 2A13 mediates the neoplastic transformation of human bronchial epithelial cells at a low concentration of aflatoxin B1

Cited by 35 publications

References 36 publications

How does airway exposure of aflatoxin B1 affect serum albumin adduct concentrations? Evidence based on epidemiological study and animal experimentation

How does airway exposure of aflatoxin B1 affect serum albumin adduct concentrations? Evidence based on epidemiological study and animal experimentation

Caffeic acid ameliorates colitis in association with increasedAkkermansiapopulation in the gut microbiota of mice

Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells

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