Dialkylnitrosamine bioactivation and carcinogenesis

Lai, David Y.; Arcos, Joseph C.

doi:10.1016/0024-3205(80)90379-3

Cited by 96 publications

(24 citation statements)

References 72 publications

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“…However, when DEN is given to male mice that are older than 4 weeks of age, it is no longer effective in HCC induction on its own and requires assistance from other tumor promoters, such as phenobarbitol. This agedependent difference in carcinogenic efficacy is not likely to be due to altered metabolic activation of DEN [36,37]. The main reason that DEN is not a complete carcinogen in mice that are more than 4 weeks old is the nearly complete absence of proliferating hepatocytes [38].…”

Section: Hepatocyte Ikk-dependent Nf-κb Signaling Suppresses Liver Camentioning

confidence: 99%

NF-κB and STAT3 – key players in liver inflammation and cancer

2010

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Hepatocellular carcinoma (HCC), the major form of primary liver cancer, is one of the most deadly human cancers. The pathogenesis of HCC is frequently linked with continuous hepatocyte death, inflammatory cell infiltration and compensatory liver regeneration. Understanding the molecular signaling pathways driving or mediating these processes during liver tumorigenesis is important for the identification of novel therapeutic targets for this dreadful disease. The classical IKKβ-dependent NF-κB signaling pathway has been shown to promote hepatocyte survival in both developing and adult livers. In addition, it also plays a crucial role in liver inflammatory responses by controlling the expression of an array of growth factors and cytokines. One of these cytokines is IL-6, which is best known for its role in the liver acute phase response. IL-6 exerts many of its functions via activation of STAT3, a transcription factor found to be important for HCC development. This review will focus on recent studies on the roles of NF-κB and STAT3 in liver cancer. Interactions between the two pathways and their potential as therapeutic targets will also be discussed.

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Section: Hepatocyte Ikk-dependent Nf-κb Signaling Suppresses Liver Camentioning

confidence: 99%

NF-κB and STAT3 – key players in liver inflammation and cancer

2010

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“…NDMA the simplest and most widely occurring nitrosamine, is reported to be acute hepatotoxic and potentially carcinogenic in various animal species including humans (Lai et al, 1980;Robbiano et al, 1996;IARC 1998). Studies have described the ability of NDMA to induce DNA damage in the primary culture of human hepatocytes (Martelli et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

N-Nitrosodimethylamine in the Kashmiri Diet and Possible Roles in the High Incidence of Gastrointestinal Cancers

Chikan

Shabir²,

Shaffi³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The Kashmiri population is culturally distinct with special dietary features owing to the temperate climatic conditions of Kashmir valley. This has habituated the population to preserve food in smoked, pickled and sundried forms which include considerable amounts of N-nitroso compounds (NOCs). These are known to cause cytotoxicity, DNA damage, mutation, unscheduled DNA synthesis and DNA methylation. All of these changes at molecular level are known to contribute to the pathogenesis of cancer. One of the prominent NOCs found in Kashmiri food is N-Nitrosodimethylamine (NDMA). Here we review the occurrence of NDMA in sundried foods, dried fish, kehwa, traditional pickle, Brassica oleracia and tobbaco. We also discuss its possible role in the high prevalence of gastrointestinal cancers in Kashmir.

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“…Bioactivation of nitrosamines can produce reactive intermediates, which can react with nucleophilic nitrogen and oxygen atoms in DNA (10). A number of DNA adducts could be formed, including those alkylated at the O position of thymine as well as the phosphodiester backbone (11,12).…”

Section: Introductionmentioning

confidence: 99%

Repeated Measurements of Urinary Methylated/Oxidative DNA Lesions, Acute Toxicity, and Mutagenicity in Coke Oven Workers

Chao¹,

Wang

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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We conducted a repeated-measures cohort study of coke oven workers to evaluate the relationships between the traditional exposure biomarker, urinary 1-hydroxypyrene (1-OHP), and a series of biomarkers, including urinary 8-oxo-7,8-dihydro-2 ¶-deoxyguanosine (8-oxodG), N7-methylguanine (N7-MeG), acute toxicity, and mutagenicity. A total of eight spot urine samples were collected from each high-exposed (at topside oven area) and low-exposed workers (at side oven area) during the whole working cycle, which consisted of 6 consecutive days of working followed by 2 days off. Our results showed that the high-exposed workers had significantly higher urinary levels of 1-OHP, 8-oxodG, and N7-MeG compared with the low-exposed workers. Acute toxicity and mutagenicity of urine were also found to be markedly increased in the high-exposed workers, as determined by Microtox assay and Ames test, respectively. Multivariate regressions analysis revealed that the urinary 8-oxodG, N7-MeG, or acute toxicity was significantly correlated with 1-OHP concentrations. Overall, the present study showed that exposure to coke oven emissions increased oxidatively damaged DNA products and mutagenicity of urine, and for the very first time, such exposure was also found to increase DNA methylation and urinary acute toxicity. The potential source of methylating agents in coke oven emissions warrants further investigation. Additionally, with repeated measurements, the pattern of time course for urinary 1-OHP was found to be different from those of 8-oxodG and N7-MeG, as well as acute toxicity and mutagenicity. This finding implies that the single measurement that was often conducted in occupational healthy investigations should be used with certain precautions, because single measurement may fail to provide the proper information of interest. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3381 -9)

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Dialkylnitrosamine bioactivation and carcinogenesis

Cited by 96 publications

References 72 publications

NF-κB and STAT3 – key players in liver inflammation and cancer

NF-κB and STAT3 – key players in liver inflammation and cancer

N-Nitrosodimethylamine in the Kashmiri Diet and Possible Roles in the High Incidence of Gastrointestinal Cancers

Repeated Measurements of Urinary Methylated/Oxidative DNA Lesions, Acute Toxicity, and Mutagenicity in Coke Oven Workers

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