Potent aneugenicity of 1-methylpyrene in human cells dependent on metabolic activation by endogenous enzymes

Li, Zihuan; Yu, Hang; Song, Meiqi; Glatt, Hansruedi; Li, Jianjun; Liu, Yungang

doi:10.1007/s00204-020-02933-w

Cited by 5 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Micronucleus Test. The micronucleus test was performed as previously described, 60 with modifications taking into account the pretreatment and the use of modulators, as described in the Cytotoxicity Assay section. In brief, HepG2 cells were seeded into 12.5 cm 2 flasks at a density of 1 × 10 5 / flask, each containing 2 mL of the medium.…”

Section: ■ Introductionmentioning

confidence: 99%

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Song

et al. 2021

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

Bisphenol (BP) compounds are endocrine-disrupting organic pollutants. BPs may increase the messenger RNA (mRNA) transcripts of nuclear receptors (NRs) regulating the expression of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes. Their impact on the genotoxicity of metabolically activated carcinogens, however, remains unknown. In this study, effects of the bisphenols A, F, S, and AF on the expression of the aryl hydrocarbon receptor (AhR), the pregnane X receptor (PXR), the constitutive androstane receptor, and individual xenobiotic-metabolizing CYP enzymes in a human hepatoma (HepG2) cell line were investigated, along with in silico binding studies of BPs to each receptor. The results indicated that each BP at 1 to 100 nM concentrations increased the mRNA transcripts and protein levels of AhR, PXR, CYP1A1, 1A2, 1B1, 2E1, and 3A4. The predicted affinities of the BPs for binding AhR were comparable to those of potent agonists. Pretreatment of HepG2 cells with each BP potentiated the induction of micronuclei by benzo[a]pyrene, aflatoxin B1, benzene, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; this effect was abolished/reduced by inhibitors of NRs and/or CYPs. Our study suggests that BPs at human exposure levels may aggravate chromosome damage by several impactful carcinogens in human cells by inducing relevant CYP enzymes, mostly via NR modulation.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Song

et al. 2021

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Goat anti-mouse IgG antibodies (DyLight 800, AB2015) and goat anti-rabbit IgG antibodies (DyLight 680, AB2013) were from Amyjet Scientific (Wuhan, China). These antibodies (from the same sources as above) worked well previously in our relevant studies. ,, …”

Section: Methodsmentioning

confidence: 59%

“…These antibodies (from the same sources as above) worked well previously in our relevant studies. 23,27,28 Cell Line. The HepG2 cell line was obtained from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China).…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The effect of BPs on the structure of mitotic spindles and centrioles in the mitosis of HepG2 cells was visualized according to our recent description. 27 Briefly, HepG2 cells were exposed to BPs using the same concentrations, positive controls, modulators, and treatment regimes as described in the section for CENP-B immunofluorescence assay. Three replicates were set up in each treatment.…”

Section: Environmental Science and Technologymentioning

confidence: 99%

See 1 more Smart Citation

Impact of Extended and Combined Exposure of Bisphenol Compounds on Their Chromosome-Damaging Effect─Increased Potency and Shifted Mode of Action

Liu

2022

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

Bisphenol (BP) compounds are important environmental pollutants and endocrine disruptors. BPs are capable of inducing DNA/ chromosome breaks (clastogenesis, involved in carcinogenesis), which requires activation by human CYP1A1. We hypothesized that combined BPs and extended (from the standard two-cell cycle) exposure may enhance their genotoxicity via modulating CYP enzymes. In this study, individual and combined BPA/BPF/BPS/BPAF and a human hepatoma (HepG2) cell line were used for testing several genotoxicity end points. Exposing for a two-cell cycle period (48 h), each BP alone (0.625−10 μM) was negative in the micronucleus test, while micronucleus was formed under three-(72 h) and four-cell cycle (96 h) exposure; BP combinations further elevated the potency (with nanomolar thresholds). Immunofluorescence analysis of the centromere with formed micronucleus indicated that 48 h exposure produced centromere-negative micronucleus and phosphorylated histone H2AX (γ-H2AX) (evidencing clastogenesis), while extended (72 and 96 h) exposure formed centromere-positive micronucleus and phosphorylated histone H3 (p-H3) (indicating chromosome loss, i.e., aneugenesis); moreover, 1-aminotriabenzotriazole (CYP inhibitor) selectively blocked the formation of centromere-negative micronucleus and γ-H2AX, without affecting that of centromere-positive micronucleus and p-H3. This study suggests that the genotoxicity of BPs is potentiated by combined and extended exposure, the latter being specific for aneuploidy formation, a CYP activity-independent effect.

show abstract

Human CYP enzyme-activated genotoxicity of 2,2′,4,4′-tetrabromobiphenyl ether in mammalian cells

et al. 2022

View full text Add to dashboard Cite

Potent aneugenicity of 1-methylpyrene in human cells dependent on metabolic activation by endogenous enzymes

Cited by 5 publications

References 38 publications

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Influence of Bisphenol Compounds at Nanomolar Concentrations on Chromosome Damage Induced by Metabolically Activated Carcinogens in HepG2 Cells

Impact of Extended and Combined Exposure of Bisphenol Compounds on Their Chromosome-Damaging Effect─Increased Potency and Shifted Mode of Action

Human CYP enzyme-activated genotoxicity of 2,2′,4,4′-tetrabromobiphenyl ether in mammalian cells

Contact Info

Product

Resources

About