In vitro genotoxicity of dibutyl phthalate on <scp>A549</scp> lung cells at air–liquid interface in exposure concentrations relevant at workplaces

Binder, Stefanie Petrou; Cao, Xin; Bauer, Stefanie; Rastak, Narges; Kuhn, Evelyn M.; Dragan, George C.; Monsé, Christian; Ferron, G.A.; Breuer, D.; Oeder, Sebastian; Karg, Erwin; Sklorz, Martin; Bucchianico, Sebastiano Di; Zimmermann, Ralf

doi:10.1002/em.22464

Cited by 11 publications

(9 citation statements)

References 58 publications

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“…Phthalates are conservational compounds and are recognized as endocrine disruptors and peroxisome proliferators (PPs) [ 2 ]. Phthalates are involved in carcinogenesis and pulmonary disorders [ 3 ]. In vivo and epidemiological studies associated structural impairment of the lung with phthalate exposure [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Cytotoxic, Genotoxic, and Oxidative Stress of Dibutyl Phthalate on Cultured Bovine Peripheral Lymphocytes

Ali

Sahar

Firyal

et al. 2022

Oxidative Medicine and Cellular Longevity

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Recently, there have been numerous reports showing that phthalates have negative human health impacts and may cause several diseases such as asthma, breast cancer, obesity, type II diabetes, and male infertility. Animals are also exposed to phthalates through the environment and can cause adverse health effects on them. Several studies have been found on the cytogenetic effects of dibutyl phthalate (DBP) on different organisms but no documented evidence has been found on the cytotoxic and genotoxic effects of dibutyl phthalate (DBP) on bovine cultured lymphocytes. MTT assay was performed on different series of DBP concentrations (10 μM, 20 μM, 30 μM, 50 μM, 70 μM, 100 μM). A concentration-dependent decrease in cell viability was observed by the DBP. The LD50, LD50/2, and 2 ∗ LD50 were found to be 50 μM, 30 μM, and 80 μM on bovine lymphocytes, respectively. Then, these concentrations of DBP were utilized to perform comet, micronucleus assays, and oxidative stress. A concentration-dependent increase in DNA damage, oxidative stress, and micronuclei formation was observed in lymphocytes by the DBP as compared to the control group. Highest genotoxic effects were observed at a concentration of 2 ∗ LD50. Similarly, total oxidative stress was found higher, and antioxidative stress was lower in concentration-dependent manner by the DBP. The current study revealed a significant cytotoxic, genotoxic, and oxidative stress of DBP on cultured bovine lymphocytes.

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Section: Introductionmentioning

confidence: 99%

Assessment of Cytotoxic, Genotoxic, and Oxidative Stress of Dibutyl Phthalate on Cultured Bovine Peripheral Lymphocytes

Ali

Sahar

Firyal

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In regard to concentrations, the maximum concentration tested was 300 µg/mL [ 31 ], with the majority of assessment performed in a range up to 100 µg/mL. For the plasticizers, their concentrations varied from 1–100 μM for DEHP and for MEHP [ 36 ] and 0.03–20 ng/cm 2 for DBP [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

“…The study of apoptotic markers in lung cells exposed to NPs and plasticizers verified the disturbance of the mitochondrial membrane potential [ 31 , 33 ]. It was also observed that the alteration ATP production and deregulation of the energy production mechanism [ 33 , 35 ] contributed towards cell damage [ 17 , 20 , 37 ]. Consequently, cell death has been reported [ 17 , 49 ] particularly for long exposure periods [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity Assessment of Nanoplastics and Plasticizers Exposure in In Vitro Lung Cell Culture Systems—A Systematic Review

Clérigo

Ferreira

Ladeira

et al. 2022

Toxics

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Emerging contaminants such as nanoplastics (NPs), as well as manufacturing by-products such as plasticizers, have gained global attention and concern due to their limited biodegradability and their potential impact on human health, in particular the effects on respiratory tissue. In parallel, in vitro cell culture techniques are key to the assessment and characterization of toxic effects and cellular mechanisms in different types of tissues and should provide relevant information to understand the hazardous potential of these emergent contaminants. This systematic review presents the main results on the current knowledge of the effects of NPs and plasticizers on lung cells, as assessed with the use of in vitro cell culture techniques. From the selected studies (n = 10), following the PRISMA approach, it was observed that cell viability was the most frequently assessed endpoint and that most studies focused on epithelial cells and exposures to polystyrene (PS). It was observed that exposure to NPs or plasticizers induces cytotoxicity in a dose-dependent manner, regardless of the size of the NPs. Furthermore, there is evidence that the characteristics of NPs can affect the toxic response by promoting the association with other organic compounds. As such, further in vitro studies focusing on the combination of NPs with plasticizers will be essential for the understanding of mechanisms of NPs toxicity.

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“…Genotoxicity was further tested at the chromosomal level by the micronucleus assay. Few studies have applied the micronucleus assay on advanced human lung models at the ALI; at the time of writing, we found only one publication on monocultured A549 [ 49 ], one on monocultured BEAS-2B and other bronchial cell types [ 59 ], and four studies on nasal epithelial cells from donors [ 60 , 61 , 62 , 63 ]. We successfully employed this assay to both mono- and cocultures of BEAS-2B cells exposed at the ALI.…”

Section: Discussionmentioning

confidence: 99%

“…Mitomycin-C (catalog no. A2190.0002, PanReac AppliChem [VWR/Avantor]) was used as a positive control for micronuclei induction in the micronucleus assay, with stock solution at 0.2 mg/mL in dimethyl sulfoxide (DMSO) stored at −20 °C, and exposure concentration at 0.15 µg/mL, similarly to Reference [ 49 ]. In one experiment with A549/EA.hy926 and BEAS-2B/EA.hy926 cocultures, a higher concentration (0.30 µg/mL) was additionally included.…”

Section: Methodsmentioning

confidence: 99%

Different Sensitivity of Advanced Bronchial and Alveolar Mono- and Coculture Models for Hazard Assessment of Nanomaterials

et al. 2023

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For the next-generation risk assessment (NGRA) of chemicals and nanomaterials, new approach methodologies (NAMs) are needed for hazard assessment in compliance with the 3R’s to reduce, replace and refine animal experiments. This study aimed to establish and characterize an advanced respiratory model consisting of human epithelial bronchial BEAS-2B cells cultivated at the air–liquid interface (ALI), both as monocultures and in cocultures with human endothelial EA.hy926 cells. The performance of the bronchial models was compared to a commonly used alveolar model consisting of A549 in monoculture and in coculture with EA.hy926 cells. The cells were exposed at the ALI to nanosilver (NM-300K) in the VITROCELL® Cloud. After 24 h, cellular viability (alamarBlue assay), inflammatory response (enzyme-linked immunosorbent assay), DNA damage (enzyme-modified comet assay), and chromosomal damage (cytokinesis-block micronucleus assay) were measured. Cytotoxicity and genotoxicity induced by NM-300K were dependent on both the cell types and model, where BEAS-2B in monocultures had the highest sensitivity in terms of cell viability and DNA strand breaks. This study indicates that the four ALI lung models have different sensitivities to NM-300K exposure and brings important knowledge for the further development of advanced 3D respiratory in vitro models for the most reliable human hazard assessment based on NAMs.

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In vitro genotoxicity of dibutyl phthalate on A549 lung cells at air–liquid interface in exposure concentrations relevant at workplaces

Cited by 11 publications

References 58 publications

Assessment of Cytotoxic, Genotoxic, and Oxidative Stress of Dibutyl Phthalate on Cultured Bovine Peripheral Lymphocytes

Assessment of Cytotoxic, Genotoxic, and Oxidative Stress of Dibutyl Phthalate on Cultured Bovine Peripheral Lymphocytes

Cytotoxicity Assessment of Nanoplastics and Plasticizers Exposure in In Vitro Lung Cell Culture Systems—A Systematic Review

Different Sensitivity of Advanced Bronchial and Alveolar Mono- and Coculture Models for Hazard Assessment of Nanomaterials

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