DNA Adducts: Endogenous and Induced

Povey, Andrew C.

doi:10.1177/019262330002800308

Cited by 55 publications

(38 citation statements)

References 68 publications

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“…Endogenous adducts, oxidative DNA damage and indirect action It has been suggested that damage to DNA from endogenous exposures may be orders of magnitude greater than those from exogenous sources including exposure to tobacco smoke (Povey, 2000). This does not imply, however, that endogenous agents do not play a role in tobacco carcinogenesis, because tobacco exposures can directly and indirectly increase oxidative stress.…”

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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“…With the potent alkylating agent, ethyl methanesulfonate, doses of 100 and 50 mg/kg, which produce alkylation of sperm DNA at the level of about 2 ethylations per 10 5 nucleotides and 5 ethylations per 10 6 nucleotides, respectively 63 , did not produce mutations 64 . This DNA alteration is about the same level as endogenous modification of DNA 39,40,65,66 . U n e x c i s e d D N A a d d u c t s i n c r i t i c a l s i t e s i n transcriptionally active DNA become promutagenic only when the cell divides.…”

Section: Mutagenesismentioning

confidence: 84%

“…A critical issue is the level at which DNA adducts have biological significance. Mammalian DNA has a high level of spontaneous modification [37][38][39][40] , in the order of about 1 lesion per 10 6 bases. Thus, the abovementioned chemical adducts levels are 10 to 100-fold lower than the spontaneous level of alteration.…”

Section: Dna Binding and Repairmentioning

confidence: 99%

Thresholds for DNA-Reactive (Genotoxic) Organic Carcinogens

2005

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“…DNA adducts have been assessed and quantified in almost all human tissues, but the preferred samples of study are white blood cells due to their availability, and lung tissue because the lung is the point of entry for most carcinogenic environmental contaminants (26). DNA adducts are evaluated by three main methodological approaches, all characterized by their sensitivity, specificity, cost and instrumentation (19).…”

Section: Dna Adductsmentioning

confidence: 99%

Molecular biomarkers to assess health risks due to environmental contaminants exposure

Poblete-Naredo

Albores

2016

biomedica

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<p>Los biomarcadores, o bioindicadores, son herramientas métricas que, al compararse con los valores de referencia, permiten evaluar los riesgos y generar información objetiva que ayude a las autoridades a planificar estrategias efectivas, solucionar problemas de salud o ambientales y utilizar los recursos asignados de manera eficiente.<br />La evaluación de riesgos en salud es un ejercicio multidisciplinario y la biología molecular contribuye enormemente a estos estudios, dado que el genoma, el transcriptoma, el proteoma y el metaboloma pueden verse afectados por xenobióticos, lo que causa cambios cuya medición resulta útil en la adopción de decisiones. Dichos cambios pueden variar por la carga genética de cada individuo y su distribución polimorfa en las poblaciones expuestas se convierte en un factor esencial para una adecuada interpretación de resultados.<br />Por lo tanto, el objetivo del presente artículo fue hacer una revisión de los diferentes biomarcadores moleculares aplicables a la evaluación de riesgos para la salud provenientes de los contaminantes ambientales.</p>

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DNA Adducts: Endogenous and Induced

Abstract: ABSTRACT

Cited by 55 publications

References 68 publications

DNA adduct burden and tobacco carcinogenesis

DNA adduct burden and tobacco carcinogenesis

Thresholds for DNA-Reactive (Genotoxic) Organic Carcinogens

Molecular biomarkers to assess health risks due to environmental contaminants exposure

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