Abundant lipophilic DNA adducts in human tissues

Ke, Yang; Fang, Jia Long; Hemminki, Kari

doi:10.1016/s0027-5107(98)00210-3

Cited by 9 publications

(3 citation statements)

References 25 publications

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“…The DNA adducts formed in reactions with carcinogenic aldehydes may produce structurally unique adducts (Hecht et al, 2001); these hold promise as sensitive markers of oral cancer risk associated with tobacco use (Nath et al, 1998). Some endogenously derived DNA adducts are thought to increase with age (Josyula et al, 2000;Yang et al, 1998). Several reviews have been presented on endogenous DNA adducts and cancer risk (Burcham, 1998;Bartsch and Nair, 2001;Blair, 2001).…”

Section: Emerging Issues In Tobacco Carcinogenesis and Dna Adductsmentioning

confidence: 99%

DNA adduct burden and tobacco carcinogenesis

Wiencke

2002

Oncogene

149

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DNA adducts associated with tobacco smoking could provide a marker of biologically effective dose of tobacco carcinogens and improve individual cancer risk prediction. A significant number of clinical and epidemiologic studies have reported associations of increased DNA adduct levels with the occurrence of the prevalent tobacco related cancers including cancer of the lung, head and neck, and bladder. The inducibility of DNA adducts following in vitro treatments using blood lymphocytes also appears to be a risk factor in the development of lung and head and neck cancer. Corroborative evidence pointing to the importance of DNA adducts in tobacco carcinogenesis include numerous studies showing associations of tobacco smoke exposure with the induction of DNA adducts in humans in vivo. Further effort is necessary, however, to more fully characterize the dose -response relationship between smoking and DNA adducts in exposed target and surrogate tissues. The relationship between gene polymorphisms thought to modify tobacco-related cancer risk and DNA adduct levels is complex. Results of some DNA adduct studies (both in vitro and in vivo) appear inconsistent with the epidemiologic findings. This is evident for polymorphisms involving both carcinogen metabolism (e.g. GSTP1) and DNA repair (e.g. XRCC1). Molecular studies of human tumors suggest associations of p53 mutation with DNA adducts and have revealed correlations of DNA adduct levels with somatic alterations (e.g. 3p21 LOH) that are thought to occur at the very earliest stages of tobacco carcinogenesis. More research is needed to assess the relationship between endogenous sources of DNA adducts and tobacco smoke exposure and the relative oncogenic effects of chemically stable versus unstable DNA adducts. Many potentially fruitful new avenues of cancer research are emerging that integrate DNA adduct analyses with assessments of smoking, genetics, diet and ambient air quality. These investigations aim to understand the multifactorial nature of interindividual variability in response to tobacco carcinogens. As these trends continue a variety of innovative study designs and approaches will become important in human populations.

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Section: Emerging Issues In Tobacco Carcinogenesis and Dna Adductsmentioning

confidence: 99%

DNA adduct burden and tobacco carcinogenesis

Wiencke

2002

Oncogene

149

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“…Susceptibility polymorphisms in the phase I 55 and phase D 56 -57 biotransforming systems have been assessed with regard to their role in modulating both DNA adduct levels and CS-related cancer incidences. Although these and several other studies have focused on considerations of CS-derived adducts 58 " 60 , surrogate markers which are presumably related to early stages of CS-related carcinogenesis (although this link needs to be more firmly established), few studies have addressed how dietary antioxidants might influence adduct formation and healthrelated outcomes. Surprisingly, recent data have shown that CS-related DNA damage may be involved in coronary artery disease 61 .…”

Section: Cigarette Smoke and Cancermentioning

confidence: 99%

Micronutrient antioxidants and smoking

Cross

Traber

Eiserich

et al. 1999

British Medical Bulletin

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Cigarette smoking is a major risk factor in such human diseases as cardiovascular disease (especially atherosclerosis), lung cancer (the leading world-wide cancer killer), and chronic obstructive pulmonary disease (COPD). An avalanche of studies has suggested that a diet rich in fruit and vegetables is associated with decreased risk for atherosclerosis and cancer. However, the dietary intake of fruits and vegetables, as well as antioxidant micronutrients, is decreased in smokers. This, along with evidence of increased utilization of ascorbic acid and alpha-tocopherol, possibly on the basis of increased oxidative stress, contributes to the low plasma antioxidant concentrations seen in many smokers. This review addresses selected mechanistic considerations of this relationship.

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“…4-Hydroxy-2-nonenal (HNE), is a major lipid peroxidation product formed by the reaction of reactive oxygen or nitrogen species with arachidonic acid in cellular membranes during exposure to tobacco smoke, inflammation, and in chronic obstructive pulmonary disease [15, 16]. The physiological concentration of HNE in the plasma is reportedly 0.3–0.7 μM [17, 18] but its concentration can approach millimolar in plasma membranes under conditions of oxidative stress [19–21].…”

Section: Introductionmentioning

confidence: 99%

The role of c-Jun phosphorylation in EpRE activation of phase II genes

Levy

Jaiswal

Forman

2009

Free Radical Biology and Medicine

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The transcription factors that bind to EpRE elements play a key role in the regulation of phase II genes. In this study, we examined whether c-Jun, a partner of Nrf2 in binding to EpRE, requires phosphorylation by JNK for binding and transcriptional activation. We used chromatin immunoprecipitation assays (ChIP) to measure recruitment of transcription factors to EpRE sequences in nqo2, gclc and gclm, western analysis for phosphorylation of JNK, and EpRE driven reporters along with a JNK specific inhibitor peptide to determine the potential importance of c-Jun phosphorylation. Human bronchial epithelial (HBE1) and human hepatoma (HepG2) cells were exposed to 4-hydroxy-2-nonenal (HNE) and differences in regulation of the same EpRE sequences examined. We found binding of c-Jun to EpRE sequences increased subsequent to HNE exposure in HepG2 cells; however, in HNE-exposed HBE1 cells, binding of only phosphorylated c-Jun to the three EpRE sequences increased. Despite the increase in binding of phosphorylated c-Jun, reporter assays for EpREs showed that inhibition of c-Jun phosphorylation had variable effects on basal and HNE-induced transcription of gclc and gclm in HBE1 cells. Thus, in terms of its role in mediating HNE-induction of EpRE-mediated transcription, c-Jun appears to be a partner of Nrf2 and while its phosphorylated form may predominate in one cell type versus another, the effect of phosphorylation of c-Jun on transcription can vary with the gene. This contrasts markedly with the well-established requirement for phosphorylation of c-Jun in the activation of AP-1/TRE mediated transcription.

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Abundant lipophilic DNA adducts in human tissues

Cited by 9 publications

References 25 publications

DNA adduct burden and tobacco carcinogenesis

DNA adduct burden and tobacco carcinogenesis

Micronutrient antioxidants and smoking

The role of c-Jun phosphorylation in EpRE activation of phase II genes

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