Significance E-cigarette smoke (ECS) delivers nicotine through aerosols without burning tobacco. ECS is promoted as noncarcinogenic. We found that induces DNA damage in mouse lung, bladder, and heart reduces DNA-repair functions proteins lung. Nicotine its nitrosation product 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same effects enhance mutations tumorigenic cell transformation cultured human lung bladder cells. These results indicate occurs heart, products are further...

Melanomas occur mainly in sunlight-exposed skin. Xeroderma pigmentosum (XP) patients have 1,000-fold higher incidence of melanoma, suggesting that sunlight-induced “bulky” photoproducts are responsible for melanomagenesis. Sunlight induces a high level reactive oxygen species melanocytes (MCs); oxidative DNA damage (ODD) may thus also contribute to melanomagenesis, and XP gene products participate the repair ODD. We examined effects melanin on UVA (320–400 nm) irradiation-induced ODD UV...

Acrolein (Acr), a ubiquitous environmental contaminant, is human carcinogen. Acr can react with DNA to form mutagenic α- and γ-hydroxy-1, N2-cyclic propano-2′-deoxyguanosine adducts (α-OH-Acr-dG γ-OH-Acr-dG). We demonstrate here that Acr-dG be efficiently repaired by the nucleotide excision repair (NER) pathway in normal bronchial epithelia (NHBE) lung fibroblasts (NHLF). However, same were poorly processed cell lysates isolated from Acr-treated NHBE NHLF, suggesting inhibits NER. In...

Abstract Activated epidermal growth factor receptor (EGFR) has been proposed in the pathophysiology of neurodegenerative diseases. In present study, anti-inflammatory effect afatinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKIs) was investigated using CTX-TNA2 cells and primary cultured astrocytes subjected to oxygen/glucose deprivation (OGD). We found that OGD induced EGFR phosphorylation activated subsequent signaling pathways, including AKT extracellular signal-regulated kinases (ERK)....

Acrolein (Acr) is a major toxicant in cigarette smoke (CS); it can interact with DNA forming two adduct isomers: α-OH-Acr-dG and γ-OH-Acr-dG. Previously, we found that the Acr-DNA binding pattern human p53 gene coincides mutational CS-related lung cancer; hence, proposed Acr cancer etiological agent [Feng, Z., Hu, W., Y., Tang, M.-s. (2006) cigarette-related agent: Preferential at hotspots inhibition of repair. Proc. Natl. Acad. Sci. U.S.A. 103, 15404−15409]. This hypothesis has been brought...

// Mao-Wen Weng 1, * , Hyun-Wook Lee Bongkun Choi Hsiang-Tsui Wang Yu Hu 1 Manju Mehta Dhimant Desai 2 Shantu Amin Yi Zheng Moon-Shong Tang Departments of Environmental Medicine, Pathology and New York University School Tuxedo, NY 10987, USA Department Pharmacology, Penn State College Hershey, PA 17033, These authors have contributed equally to this work Correspondence to: Tang, email: moon-shong.tang@nyumc.org Keywords: aflatoxin B1, hepatocellular carcinoma, p53 codon 249 mutations,...

// Hyun-Wook Lee 1,* , Hsiang-Tsui Wang Mao-wen Weng 1 Yu Hu Wei-sheng Chen David Chou Yan Liu 2 Nicholas Donin William C. Huang Herbert Lepor Xue-Ru Wu Hailin 3 Frederick A. Beland 4 and Moon-shong Tang Department of Environmental Medicine, New York University School Tuxedo Park, Urology, York, The State Key Laboratory Chemistry Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy Beijing 100085, China Division Biochemical Toxicology, National Toxicological...

// Hyun-Wook Lee 1, * , Hsiang-Tsui Wang Mao-wen Weng Chiu Chin 1 William Huang 2 Herbert Lepor Xue-Ru Wu N. Rom 3 Lung-Chi Chen Moon-shong Tang 3, 4 Department of Environmental Medicine, New York University School York, NY, USA Urology, Pathology, These authors have contributed equally to this work Correspondence to: Tang, e-mail: moon-shong.tang@nyumc.org Keywords: second-hand and side-stream smoke, acrolein BPDE, DNA damage repair, lung bladder cancer, anchorage independent growth...

Acrolein (Acr), a highly reactive unsaturated aldehyde, can cause various lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and cancer. We have found that Acr damage not only genomic DNA but also repair proteins causing dysfunction enhancing cells' mutational susceptibility. While these effects may account for carcinogenicity, the mechanisms by which induces other than cancer are unclear. In this study, we damages in mitochondrial (mtDNA), inhibits bioenergetics,...

Acrolein (Acr) is a potent cytotoxic and DNA damaging agent which ubiquitous in the environment abundant tobacco smoke. Acr also an active metabolite of anti-cancer drugs cyclophosphamide ifosfamide. The mechanisms via exerts its activity cytotoxicity are not clear. In this study, we found that induces cell death human cancer cells with different activities p53. preferentially binds nucleolar ribosomal (rDNA) to form Acr-deoxyguanosine adducts, oxidative damage both rDNA RNA (rRNA). triggers...

Alzheimer's disease (AD) is a detrimental neurodegenerative disease, and early diagnosis appears to be the key successful treatment. Acrolein, byproduct of lipid peroxidation, has been shown contribute pathological process AD. This study recruited 118 elderly subjects consisting 58 non-demented control 62 AD patients. We analyzed acrolein-related metabolites in plasma, cerebrospinal fluid (CSF), urine all subjects. found that levels acrolein-conjugated protein (Acr-PC) plasma (p = 0.00012)...

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these often develop brain metastasis (BM) during their disease course. The major obstacle BM is limited penetration anticancer drugs across blood-brain barrier (BBB). In present study, we utilized gefitinib-loaded liposomes with different modifications improve gefitinib delivery in...

Acrolein (Acr), an α,β-unsaturated aldehyde, is abundant in tobacco smoke and cooking exhaust fumes. Acr induces mutagenic α- γ- hydroxy-1, N2 -cyclic propano-deoxyguanosine adducts normal human bronchial epithelial cells. Our earlier work has found that Acr-induced DNA damage preferentially occurs at lung cancer p53 mutational hotspots contain CpG sites methylation enhances Acr-DNA binding these sites. Based on results, we hypothesized this enhancement of leads to cancer. In study, using a...

Abstract Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) the substantia nigra (SN) of patients with Parkinson’s disease (PD). In present study, acrolein-induced neurotoxicity nigrostriatal dopaminergic system was investigated by local infusion (15, 50, 150 nmoles/0.5 μl) SN Sprague-Dawley rats. Acrolein-induced neurodegeneration delineated reductions tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons infused as well...

Abstract Many patients with colorectal cancer do not respond to immune checkpoint blockade (ICB) therapy, highlighting the urgent need understand tumor resistance mechanisms. Recently, link between IFNγ signaling pathway integrity and ICB in microenvironment has been revealed. The immunosuppressive poses a significant challenge antitumor immunity development. Tumor-associated neutrophils found tissues exhibit an phenotype are associated patient prognosis. Neutrophil extracellular traps...

Glioblastoma (GBM), the most lethal type of brain tumor in adults, has considerable cellular heterogeneity. The standard adjuvant chemotherapeutic agent for GBM, temozolomide (TMZ), a modest response rate due to development drug resistance. Multiple studies have shown that valproic acid (VPA) can enhance GBM control and prolong survival when given conjunction with TMZ. However, beneficial effect is variable. In this study, we analyzed impact VPA on patient its possible correlation TMZ...

Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and the most frequent cause failure globally. A better understanding pathophysiology DN would lead to development novel therapeutic options. Acrolein, an α,β-unsaturated aldehyde, common dietary environmental pollutant.The role acrolein potential protective action scavengers in were investigated using high-fat diet/ streptozotocin-induced mice vitro cellular...

Acrolein (Acr) is a ubiquitous environmental pollutant found in cigarette smoke and automobile exhaust. It can also be produced endogenously by oxidation of polyunsaturated fatty acids. The Acr-derived 1,N(2)-propanodeoxyguanosine (Acr-dG) adducts DNA are mutagenic lesions that potentially involved human cancers. In this study, monoclonal antibodies were raised against Acr-dG characterized using ELISA. They showed strong reactivity specificity toward Acr-dG, weaker crotonaldehyde-...

Cigarette smoking (CS) and betel quid (BQ) chewing are two known risk factors have synergistic potential for the development of oral squamous cell carcinoma (OSCC) in Taiwan. The p53 mutation characteristics OSCC (G to A or G T mutations) similar that acrolein-induced DNA damage. Acrolein is a major cigarette-related carcinogen preferentially causes mutations inhibits repair function lung cancer. We hypothesize acrolein associated with carcinogenesis.A total 97 patients 230 healthy subjects...

Abstract Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with recurrence of Previous studies have shown that activation FGFR and HER2 signaling are involved in cancer cell proliferation drug resistance. Smoking most common etiologic risk factor cancer, there emerging evidence smoking underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, abundant tobacco smoke, cooking fumes, automobile exhaust...