Enhanced DNA adduct formation by benzo[a]pyrene in human liver cells lacking cytochrome P450 oxidoreductase

Reed, Lindsay; Jarvis, Ian; Phillips, David H.; Arlt, Volker M.

doi:10.1016/j.mrgentox.2020.503162

Cited by 12 publications

(8 citation statements)

References 35 publications

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“…Our results indicated that single treatment with low doses of UVA light (up to 1 J/cm 2 ) was not harmful, in agreement with previously published results [ 49 ]. Equally, BaP alone remained non-toxic at the concentrations selected for this study (2 µM for HaCaT cells, and 5 µM for B16-F10 cells), matching previous results generated in liver cells [ 50 , 51 ]. Importantly, we demonstrated that the sequential treatment with these non-toxic doses of BaP particles and UVA light did induce a significant decrease in cell viability in both cell lines, confirming the deleterious synergistic effect anticipated by other authors [ 52 , 53 ].…”

Section: Discussionsupporting

confidence: 88%

Protective Effect of the Hydrophilic Extract of Polypodium leucotomos, Fernblock®, against the Synergistic Action of UVA Radiation and Benzo[a]pyrene Pollutant

et al. 2022

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Oxidative stress is a harmful effect induced on the skin by polycyclic aromatic hydrocarbons (PAH), including benzo[a]pyrene (BaP) air pollutants. This effect is amplified by the additive damaging effect of the sun, especially through the UVA light component. Besides being one of the main compounds that make up air pollution, BaP can also be found in tar, tobacco smoke, and various foods. In addition to its direct carcinogenic potential, BaP can act as a photosensitizer absorbing sunlight in the UVA range and thus generating ROS and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Fernblock® (FB) is an aqueous extract from the leaves of Polypodium leucotomos that has been proven to exert photoprotective and antioxidant effects on skin cells. In this study, we evaluate the potential of FB to prevent the damage induced by a combination of BaP and UVA light on human keratinocyte and mouse melanocyte cell lines (HaCaT and B16-F10, respectively). In particular, we have analyzed the capacity of FB to counteract the alterations caused on cellular morphology, viability, oxidative stress and melanogenic signaling pathway activation. Our data indicate that FB prevented cell damage and reduced oxidative stress and melanogenic signaling pathway activation caused by a combination of BaP and UVA light irradiation. Altogether, our findings support the fact that FB is able to prevent skin damage caused by the exposure to a combination of UVA and the air pollutant BaP.

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Section: Discussionsupporting

confidence: 88%

Protective Effect of the Hydrophilic Extract of Polypodium leucotomos, Fernblock®, against the Synergistic Action of UVA Radiation and Benzo[a]pyrene Pollutant

et al. 2022

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“…BαP is an environmental and foodborne pollutant often generated during industrial processes and anthropogenic activities, including cigarette smoke, automobile emission, and culinary processes (Shiizaki et al, 2017;Reed et al, 2020). It is listed as a Group 1 carcinogen by International Agency for Research on Cancer (IARC) due to its roles as a potent mutagenic, carcinogenic, and pro-oxidative agent in experimental animals (Wester et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Ginger constituents ameliorated B(α)P-induced toxicity via modulation of antioxidants and xenobiotic-metabolising enzymes in mice

Gao¹,

Ren²,

Liu³

et al. 2022

IFRJ

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Accumulating evidence has linked benzo(α)pyrene (BαP) exposure to carcinogenesis with severe damages to reproductive, hematopoietic, hepatic, and renal tissues. Ginger (Zingiber officinale Roscoe) rhizome consumed worldwide as a spice and herbal medicine, exhibits a variety of health benefits including antioxidant, anti-inflammatory, and anti-cancer activities. In the present work, the efficacy of three ginger compounds namely 6-gingerol, zingerone, and curcumin against BαP-induced toxicity in mice was investigated. Kunming Swiss albino male mice were orally gavage with curcumin, 6-gingerol, or zingerone (all at a dose of 100 mg/kg body weight) for two weeks before intraperitoneal injection with benzo(α)pyrene (BαP) at 20 mg/kg body weight. The effect of these ginger compounds on antioxidant and xenobiotic-metabolising enzymes in vivo was investigated. Results showed that pre-treatment with curcumin, 6-gingerol, or zingerone significantly (p < 0.05) increased catalase (CAT) and glutathione peroxidase (GPx) activities in serum and liver of mice, upregulated activities of phase II enzymes (quinone reductase (QR) and glutathione-S-transferase (GST)), and their protein and mRNA levels in liver of mice; but reduced levels of activities, protein, and mRNA of phase I enzymes (CYP1A1 and CYP1A2) as compared to those of BαP-only treatment. Furthermore, these compounds significantly (p < 0.05) stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression, whilst curcumin suppressed the expression of Kelch-like ECH-associated protein 1 (Keap1) in liver. These results could contribute to our understanding of the potential beneficial effects of consuming ginger as food and/or dietary supplement.

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“…Oral B[a]P led to a slower clearance of B[a]P from the blood in CYP1A1(À/À) mice, and higher DNA adduct formation in liver intestine, spleen and bone marrow compared with wild-type mice (Uno et al, 2001). More B[a]P-DNA adduct was formed in HepG2 cells lacking CYP450 (Reed et al, 2020). B[a] P-induced DNA adduct formation was repressed in hepatocytes with CYP1A1 overexpression and was increased in CYP1A1 (À/À) mice (Endo et al, 2008) (Uno et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Alterations of DNA methylation and mRNA levels of CYP1A1, GSTP1, and GSTM1 in human bronchial epithelial cells induced by benzo[a]pyrene

Liu

Hao

et al. 2022

Toxicol Ind Health

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Benzo[a]pyrene (B[a]P) is a known human carcinogen and plays a major function in the initiation of lung cancer at its first proximity. However, the underlying molecular mechanisms are less well understood. In this study, we investigated the impact of B[a]P treatment on the DNA methylation and mRNA levels of CYP1A1, GSTP1, and GSTM1 in human bronchial epithelial cells (16HBEs), and provide scientific evidence for the mechanism study on the carcinogenesis of B[a]P. We treated 16HBEs with DMSO or concentrations of B[a]P at 1, 2, and 5 mmol/L for 24 h, observed the morphological changes, determined the cell viability, DNA methylation, and mRNA levels of CYP1A1, GSTP1, and GSTM1. Compared to the DMSO controls, B[a]P treatment had significantly increased the neoplastic cell number and cell viability in 16HBEs at all three doses (1, 2, and 5 mmol/L), and had significantly reduced the CYP1A1 and GSTP1 DNA promoter methylation levels. Following B[a]P treatment, the GSTM1 promoter methylation level in 16HBEs was profoundly reduced at low dose group compared to the DMSO controls, yet it was significantly increased at both middle and high dose groups. The mRNA levels of CYP1A1, GSTP1, and GSTM1 were significantly decreased in 16HBEs following B[a]P treatment at all three doses. The findings demonstrate that B[a]P promoted cell proliferation in 16HBEs, which was possibly related to the altered DNA methylations and the inhibited mRNA levels in CYP1A1, GSTP1, and GSTM1.

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Enhanced DNA adduct formation by benzo[a]pyrene in human liver cells lacking cytochrome P450 oxidoreductase

Cited by 12 publications

References 35 publications

Protective Effect of the Hydrophilic Extract of Polypodium leucotomos, Fernblock®, against the Synergistic Action of UVA Radiation and Benzo[a]pyrene Pollutant

Protective Effect of the Hydrophilic Extract of Polypodium leucotomos, Fernblock®, against the Synergistic Action of UVA Radiation and Benzo[a]pyrene Pollutant

Ginger constituents ameliorated B(α)P-induced toxicity via modulation of antioxidants and xenobiotic-metabolising enzymes in mice

Alterations of DNA methylation and mRNA levels of CYP1A1, GSTP1, and GSTM1 in human bronchial epithelial cells induced by benzo[a]pyrene

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