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Betel quid containing safrole enhances metabolic activation of tobacco specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
2019
Tsou, Han-Hsing | Ko, Hsiao-Tung | Chen, Chia-Tzu | Wang, Tse-Wen | Lee, Chien-Hung | Liu, Tsung-Yun | Wang, Hsiang-Tsui
Cigarette smoking (CS) and betel quid (BQ) chewing are two known risk factors that have synergistic potential for the enhancing the development of oral squamous cell carcinoma (OSCC) in Taiwan. Most mutagens and carcinogens are metabolically activated by cytochrome P450 (CYP450) to exert their mutagenicity or carcinogenicity. Previous studies have shown that metabolic activation of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by CYP2A6 activity determines NNK-induced carcinogenesis. In addition, safrole affects cytochrome P450 activity in rodents. However, the effect of BQ safrole on the metabolism of tobacco-specific NNK and its carcinogenicity remains elusive. This study demonstrates that safrole (1 mg/kg/d) induced CYP2A6 activity, reduced urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels, and increased NNK-induced DNA damage, including N7-methylguanine, 8-OH-deoxyguanosine and DNA strand breaks in a Syrian golden hamster model. Furthermore, altered NNK metabolism and increased NNK-induced DNA damage were also observed in healthy subjects with CS and BQ chewing histories compared to healthy subjects with CS histories. In conclusion, BQ containing safrole induced tobacco-specific NNK metabolic activation, resulting in higher NNK-induced genotoxicity. This study provides valuable insight into the synergistic mechanisms of CS- and BQ-induced OSCC.
显示更多 [+] 显示较少 [-]Biochemical, hematological, and pathological related healing effects of Elaeagnus angustifolia hydroalcoholic extract in 5-fluorouracil-induced oral mucositis in male golden hamster
2017
Koohi-Hosseinabadi, Omid | Ranjbar, Zahra | Sepehrimanesh, Masood | AndisheTadbir, Azadeh | Poorbaghi, Seyedeh Leila | Bahranifard, Hajar | Tanideh, Nader | Koohi-Hosseinabadi, Maryam | Iraji, Aida
Oral mucositis (OM) is one of the cancer chemotherapy-related side effects which can affect the quality of life of affected patients. This study was designed to investigate the healing effect of Elaeagnus angustifolia in 5-flurouracil (5-FU)-induced OM in golden hamster. Fifty-six adult male golden hamsters received three intraperitoneal injections of 5-FU at a dose of 60 mg/kg on days 0, 5, and 10. The cheek pouch mucosa was scratched superficially under local anesthesia. Then, two horizontal scratches were made across the everted cheek pouch on days 3 and 4. All treatments were started on day 12 for equal number of animals in control group with no treatments, gel base group that was treated with carboxy methyl cellulose as gel base which used in preparation of the topical gel, topical gel group that used gel containing 10% hydroalcoholic extract of E. angustifolia (HEEA) topically, and dietary group which was treated with 300 mg/kg HEEA. At 2 and 5 days after treatment, blood and pouch tissue sampling were done and analyzed for blood composition, tissue malondialdehyde (MDA) level, and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities plus histopathological evaluations. Both topically and orally HEEA-treated groups showed a significant relief in OM compared to the control and base gel groups. However, the systemic form had higher efficiency in some parts especially decreasing the MPO (0.27 ± 0.17 vs. 0.56 ± 0.17 IU/L) and increasing SOD (6.46 ± 0.15 vs. 5.36 ± 0.18 IU/L) activities in pouch tissue in comparison to topical form mostly at 5 days after treatment. It seems that hydroalcoholic extract of E. angustifolia can be used as an appropriate drug choice for the treatment of oral mucositis based on its healing stimulatory and anti-inflammatory properties.
显示更多 [+] 显示较少 [-]Perfluorooctanoic acid (PFOA) acts as a tumor promoter on Syrian hamster embryo (SHE) cells
2012
Jacquet, N. | Maire, M. A. | Rast, C. | Bonnard, M. | Vasseur, P.
Perfluorooctane sulfonate (PFOS) (C₈F₁₇SO₃) and perfluorooctanoic acid (PFOA) (C₈HF₁₅O₂) are synthetic chemicals widely used in industrial applications for their hydrophobic and oleophobic properties. They are persistent, bioaccumulative, and toxic to mammalian species. Their widespread distribution on earth and contamination of human serum raised concerns about long-term side effects. They are suspected to be carcinogenic through a nongenotoxic mode of action, a mechanism supported by recent findings that PFOS induced cell transformation but no genotoxicity in Syrian hamster embryo (SHE) cells. In the present study, we evaluated carcinogenic potential of PFOA using the cell transformation assay on SHE cells. The chemical was applied alone or in combination with a nontransformant concentration of benzo[a]pyrene (BaP, 0.4 μM) in order to detect PFOA ability to act as tumor initiator or tumor promoter. The results showed that PFOA tested alone in the range 3.7 × 10⁻⁵ to 300 μM did not induce SHE cell transformation frequency in a 7-day treatment. On the other side, the combination BaP/PFOA induced cell transformation at all PFOA concentrations tested, which revealed synergistic effects. No genotoxicity of PFOA on SHE cells was detected using the comet assay after 5 and 24 h of exposure. No significant increase in DNA breakage was found in BaP-initiated cells exposed to PFOA in a 7-day treatment. The whole results showed that PFOA acts as a tumor promoter and a nongenotoxic carcinogen. Cell transformation in initiated cells was observed at concentrations equivalent to the ones found in human serum of nonoccupationally and occupationally exposed populations. An involvement of PFOA in increased incidence of cancer recorded in occupationally exposed population cannot be ruled out.
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