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Downregulation of the Phosphatase PHLPP1 Contributes to NNK-induced Malignant Transformation of Human Bronchial Epithelial Cells (HBECs).

J Biol Chem

January 2025

Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University; Wenzhou, Zhejiang 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325053, China. Electronic address:

Cigarette smoking (CS) is one of the greatest health concerns, which can cause lung cancer. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, and has been well-documented for its carcinogenic activity in both epidemiological and laboratory studies. PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and phosphatase and tensin homolog (PTEN) are two well-known phosphatase tumor suppressors that have been reported to be downregulated in human lung cancer tissues.

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The toxicokinetics of nitrosamines remain a mystery to this day, though it appears that the role of nitrosamines in potentiating the generation of mutations required for the onset of skin cancer continues to be a significant concern. Nitrosamines are mutagens, genotoxic substances, and mediators of phototoxicity/carcinogenicity, whose long-term daily usage, in the context of polypharmacy, can result in the parallel appearance of heterogeneous forms of skin cancer: keratinocytic and melanocytic. But a number of clinical observations suggest that it is the nitrosamines that potentiate the multiple occurrences of skin cancer over the years, or recurrences of skin cancer localized in areas exposed to solar radiation.

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Dietary intake and risk assessment of nitrosamine in processed meat products among medical staff during their night shift.

Sci Rep

January 2025

Nutrition Department, High Institute of Public Health, Alexandria University, 165 EL-Horreya Avenue, EL-Hadarah, Alexandria, 21561, Egypt.

The study aims to evaluate the levels of nitrosamine, a known carcinogenic compound, in processed meat products and to assess its dietary intake and margin of exposure among medical staff, including physicians, pharmacists, and nurses working night shifts at Alexandria University Hospitals. Additionally, the study seeks to evaluate the participants' knowledge of dietary sources and regulatory limits of carcinogens. A cross-sectional study was conducted with 420 participants.

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Alkaloids and nitrosamines in betel quid: A biochemical exploration of carcinogenicity.

Chem Biol Interact

January 2025

Department of Community Dental Health, Faculty of Dental Sciences, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka.

Betel quid contains two major ingredients; Areca catechu and Piper betel, often consumed with slaked lime, tobacco, certain flavouring agents, colouring agents, herbs, and spices according to personal preferences. The areca nut alkaloids (arecoline, arecaidine, guvacine, and guvacoline), and tobacco alkaloids (nicotine, nornicotine) undergo nitrosation during chewing in the oral cavity with the presence of nitrite and thiocyanate and endogenously. Among the nitrosation products generated areca nut-derived nitrosamine (ADNA): 3-(methylnitrosamino) Propionitrile (MNPN) and the two tobacco-specific nitrosamines (TSNAs); N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) (NNK) are considered Group 1 human carcinogens.

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The present study investigates the influence of nitrosamines and etoposide on mesenchymal stromal cells (MSCs) in a differentiation state- and biological age-dependent manner. The genotoxic effects of the agents on both neonatal and adult stem cell populations after treatment, before, or during the course of differentiation, and the sensitivity of the different MSC types to different concentrations of MNU or etoposide were assessed. Hereby, the multipotent differentiation capacity of MSCs into osteoblasts, adipocytes, and chondrocytes was analyzed.

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