Investigating the Role of Mitochondrial Respiratory Dysfunction during Hexavalent Chromium-Induced Lung Carcinogenesis

Wise, James T.F.; Wang, Lei; Alstott, Michael; Ngalame, Ntube N. O.; Wang, Yuting; Zhang, Zhuo; Shi, Xianglin

doi:10.1615/jenvironpatholtoxicoloncol.2018028689

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…Hexavalent chromium (Cr +6 ) compounds are classified as carcinogenic to humans in the respiratory tract, giving rise to cancer of the lungs, nose, and nasal sinuses. It is mutagenic when inhaled and also potentially when ingested orally in large quantities [104,105]. In particular, in certain occupational environments, workers may suffer from inhalation exposure by Cr +6 dust, mists, and fumes [106].…”

Section: Carcinogenic Risk Assessmentmentioning

confidence: 99%

Carcinogenic Risk of Pb, Cd, Ni, and Cr and Critical Ecological Risk of Cd and Cu in Soil and Groundwater around the Municipal Solid Waste Open Dump in Central Thailand

Aendo

Netvichian

Thiendedsakul

et al. 2022

Journal of Environmental and Public Health

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Several consequences of health effects from municipal solid waste caused by carcinogenic and noncarcinogenic metals have been recognized. The water quality index ( WQI ) in the groundwater around this landfill is 2945.58, which is unacceptable for consumption. The contaminated groundwater mainly appears within a 1 km radius around the landfill. The metal pollution levels in the soil in descending order were Cu > Cd > Zn=Cr > Pb > Ni. The pollution degree (ER) of Cd was 2898.88, and the potential ecological risk index (RI) was 2945.58, indicating that the risk level was very high. Surprisingly, the hazard index (HI) of Pb (2.05) and Fe (1.59) in children was higher than 1. This indicated that the chronic risk and cancer risk caused by Pb and Fe for children were at a medium level. Carcinogenic risk by oral (CR oral) consumption of Ni, Cd, and Cr in children was 1.4E − 04, 2.5E − 04, and 1.8E − 04, respectively, while the lifetime carcinogenic risk (LCR) of Ni, Cd, and Cr in children was 1.5E − 04, 2.8E − 04, and 2.0E − 04, respectively. In adults, CR oral of Ni and Cr were 1.6E − 03 and 3.0E − 04, respectively, while LCR of Ni and Cr were 1.6E − 03 and 3.4E − 04, respectively, which exceeded the carcinogenic risks limits. Our study indicated a lifetime carcinogenic risk to humans. Environmental surveillance should focus on reducing health risks such as continuous monitoring of the groundwater, soil, and leachate treatment process.

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Section: Carcinogenic Risk Assessmentmentioning

confidence: 99%

Carcinogenic Risk of Pb, Cd, Ni, and Cr and Critical Ecological Risk of Cd and Cu in Soil and Groundwater around the Municipal Solid Waste Open Dump in Central Thailand

Aendo

Netvichian

Thiendedsakul

et al. 2022

Journal of Environmental and Public Health

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“…Since metal AM involve both ultrafine and fine metal particles, and in general similar elements as can be found in metal production environments, it could be expected that AM operators have similar exposure related health risks as other metalworkers [7,8]. For example, lung complications have been found in hard metalworkers due to cobalt, hexavalent chromium, and nickel exposure [9][10][11], which may be relevant since cobalt, nickel, and chromium (but not hexavalent) are common components in AM powders. Also, lung function and cardiovascular disease (CVD) risk among welders have been extensively studied [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Metal additive manufacturing and possible clinical markers for the monitoring of exposure-related health effects

et al. 2021

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Additive manufacturing (AM) includes a series of techniques used to create products, in several different materials, such as metal, polymer or ceramics, with digital models. The main advantage of AM is that it allows the creation of complex structures, but AM promises several additional advantages including the possibility to manufacture on demand or replacing smaller worn parts by directly building on an existing piece. Therefore, the interest for and establishment of AM is rapidly expanding, which is positive, however it is important to be aware that new techniques may also result in new challenges regarding health and safety issues. Metals in blood and possible clinical effects due to metal exposure were investigated in AM operators at one of the first serial producing AM facilities in the world during two consecutive years with implementation of preventive measures in-between. As comparison, welders and office workers as control group were investigated. Health investigations comprised of surveys, lung function tests, antioxidant activity and vascular inflammation as well as renal- and hepatic function analysis. AM operators had significantly reduced nickel levels in blood (10.8 vs 6.2 nmol/L) as well as improved lung function (80 vs 92% of predicted) from year 1 to year 2. This is in line with previously published results displaying reduced exposure. Blood cobalt and nickel levels correlated with previously reported urinary levels, while blood chromium did not. Multivariate modelling showed that blood cobalt, antioxidant/inflammatory marker serum amyloid A1/serum paraoxonase/arylesterase 1 activity and the hepatic markers aspartate transaminase, alanine transaminase, and alkaline phosphatase were higher in AM operators compared to controls. The study show that the selected clinical analyses could function as a complement to metal analyses in biological fluids when investigating exposure-related health effects in AM operators. However, validation in larger cohorts is necessary before more definite conclusions could be drawn.

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“…Both the BEP2D and Cr(VI)-transformed BEP2D cell lines were cultured in LHC-8 media. All cells were screened for growth in soft agar and in nude mice to confirm the Cr(VI)-transformed cells and passage-matched control cells; this confirmed that the passagematched control cells did not spontaneously transform [12]. Additionally, karyotypes were screened by Dr. John P. Wise, Sr. at the University of Louisville, KY to authenticate the passage-matched control cell lines.…”

Section: Cell Culturementioning

confidence: 94%

“…Using the BEAS-B cells and Cr(VI)-transformed BEAS-2B cells (B2B-CrT) from our previous study, we investigated lipogenesis endpoints in these cells (protein and functional palmitic acid levels) [12]. The B2B-CrT cells had increased ACLY, pACLY, ACC1, and FASN protein expressions compared to passage-matched control BEAS-2B cells.…”

Section: Chromium(vi)-transformed Beas-2b Cells Have Increased Lipoge...mentioning

confidence: 99%

“…To determine if the increase in FASN expression is important to Cr(VI)-transformed cell tumorigenesis, we examined the xenograft tumor development of Cr(VI)-transformed BEAS-2B cells following the loss of FASN expression using shRNA. We chose to focus on just the BEAS-2B cells, since all three cell types showed the same metabolism changes following neoplastic transformation with chromium and have all been shown to grow tumors in nude mice [12]. Following the shRNA inhibition, B2B-CrT had a loss of visible FASN expression with shFASN sequence C (Figure 5A).…”

Section: Increased Fasn Expression Is Important For Chromium(vi)-tran...mentioning

confidence: 99%

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Increased Lipogenesis Is Important for Hexavalent Chromium-Transformed Lung Cells and Xenograft Tumor Growth

Wise,

Kondo

2023

IJMS

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Hexavalent chromium, Cr(VI), is a known carcinogen and environmental health concern. It has been established that reactive oxygen species, genomic instability, and DNA damage repair deficiency are important contributors to the Cr(VI)-induced carcinogenesis mechanism. However, some hallmarks of cancer remain under-researched regarding the mechanism behind Cr(VI)-induced carcinogenesis. Increased lipogenesis is important to carcinogenesis and tumorigenesis in multiple types of cancers, yet the role increased lipogenesis has in Cr(VI) carcinogenesis is unclear. We report here that Cr(VI)-induced transformation of three human lung cell lines (BEAS-2B, BEP2D, and WTHBF-6) resulted in increased lipogenesis (palmitic acid levels), and Cr(VI)-transformed cells had an increased expression of key lipogenesis proteins (ATP citrate lyase [ACLY], acetyl-CoA carboxylase [ACC1], and fatty acid synthase [FASN]). We also determined that the Cr(VI)-transformed cells did not exhibit an increase in fatty acid oxidation or lipid droplets compared to their passage-matched control cells. Additionally, we observed increases in ACLY, ACC1, and FASN in lung tumor tissue compared with normal-adjacent lung tissue (in chromate workers that died of chromate-induced tumors). Next, using a known FASN inhibitor (C75), we treated Cr(VI)-transformed BEAS-2B with this inhibitor and measured cell growth, FASN protein expression, and growth in soft agar. We observed that FASN inhibition results in a decreased protein expression, decreased cell growth, and the inhibition of colony growth in soft agar. Next, using shRNA to knock down the FASN protein in Cr(VI)-transformed BEAS-2B cells, we saw a decrease in FASN protein expression and a loss of the xenograft tumor development of Cr(VI)-transformed BEAS-2B cells. These results demonstrate that FASN is important for Cr(VI)-transformed cell growth and cancer properties. In conclusion, these data show that Cr(VI)-transformation in vitro caused an increase in lipogenesis, and that this increase is vital for Cr(VI)-transformed cells.

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Investigating the Role of Mitochondrial Respiratory Dysfunction during Hexavalent Chromium-Induced Lung Carcinogenesis

Cited by 13 publications

References 35 publications

Carcinogenic Risk of Pb, Cd, Ni, and Cr and Critical Ecological Risk of Cd and Cu in Soil and Groundwater around the Municipal Solid Waste Open Dump in Central Thailand

Carcinogenic Risk of Pb, Cd, Ni, and Cr and Critical Ecological Risk of Cd and Cu in Soil and Groundwater around the Municipal Solid Waste Open Dump in Central Thailand

Metal additive manufacturing and possible clinical markers for the monitoring of exposure-related health effects

Increased Lipogenesis Is Important for Hexavalent Chromium-Transformed Lung Cells and Xenograft Tumor Growth

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