Human adrenocortical carcinoma cell line (NCI-H295R): An in vitro screening model for the assessment of endocrine disruptors’ actions on steroidogenesis with an emphasis on cell ultrastructural features

Ďúranová, Hana; Fialková, Veronika; Válková, Veronika; Bilčíková, Jana; Olexíková, Lucia; Lukáč, Norbert; Massányi, Péter; Knazicka, Zuzana

doi:10.1016/j.acthis.2022.151912

Cited by 9 publications

(2 citation statements)

References 88 publications

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“…In general, mitochondria are highly dynamic organelles whose unique and markedly distinguished architecture is easily recognizable in electron micrographs. Along with their versatile functionality, which is reflected in the modifications in their ultrastructural features, these organelles are considered worthwhile objects of interest in basic morphological research [180][181][182]. In plant responses and stress tolerance, mitochondria play an irreplaceable role [136], and changes in their function can also be seen in their ultrastructure.…”

Section: Mitochondriamentioning

confidence: 99%

Modifications in Ultrastructural Characteristics and Redox Status of Plants under Environmental Stress: A Review

Ďúranová

Valková

Ďurišová

et al. 2023

Plants

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The rate of global environmental change is unprecedented, with climate change causing an increase in the oscillation and intensification of various abiotic stress factors that have negative impacts on crop production. This issue has become an alarming global concern, especially for countries already facing the threat of food insecurity. Abiotic stressors, such as drought, salinity, extreme temperatures, and metal (nanoparticle) toxicities, are recognized as major constraints in agriculture, and are closely associated with the crop yield penalty and losses in food supply. In order to combat abiotic stress, it is important to understand how plant organs adapt to changing conditions, as this can help produce more stress-resistant or stress-tolerant plants. The investigation of plant tissue ultrastructure and subcellular components can provide valuable insights into plant responses to abiotic stress-related stimuli. In particular, the columella cells (statocytes) of the root cap exhibit a unique architecture that is easily recognizable under a transmission electron microscope, making them a useful experimental model for ultrastructural observations. In combination with the assessment of plant oxidative/antioxidative status, both approaches can shed more light on the cellular and molecular mechanisms involved in plant adaptation to environmental cues. This review summarizes life-threatening factors of the changing environment that lead to stress-related damage to plants, with an emphasis on their subcellular components. Additionally, selected plant responses to such conditions in the context of their ability to adapt and survive in a challenging environment are also described.

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Section: Mitochondriamentioning

confidence: 99%

Modifications in Ultrastructural Characteristics and Redox Status of Plants under Environmental Stress: A Review

Ďúranová

Valková

Ďurišová

et al. 2023

Plants

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“…Common screening methods: Effects on steroidogenesis are often analysed using the NCI-H295R cell line, which has emerged as a screening tool for adrenocortical physiology and potential endocrine disruption [94][95][96]. This is already implemented in the screening panel for the hazard identification of newly developed chemicals, proposed by the OECD and the US-EPA.…”

Section: Timementioning

confidence: 99%

Endocrine Disruptors: Focus on the Adrenal Cortex

Pötzl,

Kürzinger,

Stopper

et al. 2023

Horm Metab Res

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Endocrine-disrupting chemicals (EDCs) are exogenous substances known to interfere with endocrine homeostasis and promote adverse health outcomes. Their impact on the adrenal cortex, corticosteroids and their physiological role in the organism has not yet been sufficiently elucidated. In this review, we collect experimental and epidemiological evidence on adrenal disruption by relevant endocrine disruptors. In vitro data suggest significant alterations of gene expression, cell signalling, steroid production, steroid distribution, and action. Additionally, morphological studies revealed disturbances in tissue organization and development, local inflammation, and zone-specific hyperplasia. Finally, endocrine circuits, such as the hypothalamic-pituitary-adrenal axis, might be affected by EDCs. Many questions regarding the detection of steroidogenesis disruption and the effects of combined toxicity remain unanswered. Not only due to the diverse mode of action of adrenal steroids and their implication in many common diseases, there is no doubt that further research on endocrine disruption of the adrenocortical system is needed.

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Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates

Strand,

Nylander,

Höglund

et al. 2024

Cell Biol Toxicol

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Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant to human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled to a 96-well microplate format to screen 24 POPs for their effects on viability, and testosterone and estradiol synthesis using the human adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls and three polybrominated diphenyl ethers) were tested at human-relevant levels (1 nM to 10 µM). Increased estradiol synthesis, above the OECD guideline threshold of 1.5-fold solvent control, was shown after exposure to 10 µM PCB-156 (153%) and PCB-180 (196%). Interestingly, the base hormone synthesis varied depending on the cell batch. An alternative data analysis using a linear mixed-effects model that include multiple independent experiments and considers batch-dependent variation was therefore applied. This approach revealed small but statistically significant effects on estradiol or testosterone synthesis for 17 compounds. Increased testosterone levels were demonstrated even at 1 nM for PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), PCB-180 (22%), and PBDE-153 (21%). The MTT assay revealed significant effects on cell viability after exposure to 1 nM of perfluoroundecanoic acid (12%), 3 nM PBDE-153 (9%), and 10 µM of PCB-156 (6%). This shows that some POPs can interfere with endocrine signaling at concentrations found in human blood, highlighting the need for further investigation into the toxicological mechanisms of POPs and their mixtures at low concentrations relevant to human exposure. Graphical Abstract

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Human adrenocortical carcinoma cell line (NCI-H295R): An in vitro screening model for the assessment of endocrine disruptors’ actions on steroidogenesis with an emphasis on cell ultrastructural features

Cited by 9 publications

References 88 publications

Modifications in Ultrastructural Characteristics and Redox Status of Plants under Environmental Stress: A Review

Modifications in Ultrastructural Characteristics and Redox Status of Plants under Environmental Stress: A Review

Endocrine Disruptors: Focus on the Adrenal Cortex

Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates

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