Linking the generation of DNA adducts to lung cancer.

Worldwide, lung cancer is the leading cause of cancer death. DNA adducts are considered a reliable biomarker that reflects carcinogen exposure to tobacco smoke, but the central question is what is the relationship of DNA adducts and cancer? Therefore, we investigated this relationship by a meta-analysis of twenty-two studies with bronchial adducts for a total of 1091 subjects, 887 lung cancer cases and 204 apparently healthy individuals with no evidence of lung cancer. Our study shows that these adducts are significantly associated to increase lung cancer risk.

Bulky DNA Adducts, Tobacco Smoking, Genetic Susceptibility, and Lung Cancer Risk.

The generation of bulky DNA adducts consists of conjugates formed between large reactive electrophiles and DNA-binding sites. The term "bulky DNA adducts" comes from early experiments that employed a P-DNA postlabeling approach. This technique has long been used to elucidate the association between adducts and carcinogen exposure in tobacco smoke studies and assess the predictive value of adducts in cancer risk.

Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.

Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3)-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls.

3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers.

Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber.

8-Oxo-7,8-dihydro-2'-deoxyguanosine and other lesions along the coding strand of the exon 5 of the tumour suppressor gene P53 in a breast cancer case-control study.

The next-generation sequencing studies of breast cancer have reported that the tumour suppressor P53 (TP53) gene is mutated in more than 40% of the tumours. We studied the levels of oxidative lesions, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), along the coding strand of the exon 5 in breast cancer patients as well as in a reactive oxygen species (ROS)-attacked breast cancer cell line using the ligation-mediated polymerase chain reaction technique. We detected a significant 'in vitro' generation of 8-oxodG between the codons 163 and 175, corresponding to a TP53 region with high mutation prevalence, after treatment with xanthine plus xanthine oxidase, a ROS-generating system.

Formaldehyde-induced toxicity in the nasal epithelia of workers of a plastic laminate plant.

Formaldehyde is a ubiquitous volatile organic compound widely used for various industrial purposes. Formaldehyde was reclassified by the International Agency for Research on Cancer as a human carcinogen, based on sufficient evidence for a casual role for nasopharyngeal cancer. However, the mechanisms by which this compound causes nasopharyngeal cancer are not completely understood.

Oxidatively damaged DNA in the nasal epithelium of workers occupationally exposed to silica dust in Tuscany region, Italy.

Unlabelled: Chronic silica exposure has been associated to cancer and silicosis. Furthermore, the induction of oxidative stress and the generation of reactive oxygen species have been indicated to play a main role in the carcinogenicity of respirable silica. Therefore, we conducted a cross-sectional study to evaluate the prevalence of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and peroxidation of lipids, in the nasal epithelium of 135 silica-exposed workers, employed in pottery, ceramic and marble manufacturing plants as well as in a stone quarry, in respect to 118 controls living in Tuscany region, Italy.

Bisphenol-A exposures and behavioural aberrations: median and linear spline and meta-regression analyses of 12 toxicity studies in rodents.

Exposures to bisphenol-A, a weak estrogenic chemical, largely used for the production of plastic containers, can affect the rodent behaviour. Thus, we examined the relationships between bisphenol-A and the anxiety-like behaviour, spatial skills, and aggressiveness, in 12 toxicity studies of rodent offspring from females orally exposed to bisphenol-A, while pregnant and/or lactating, by median and linear splines analyses. Subsequently, the meta-regression analysis was applied to quantify the behavioural changes.

Aromatic adducts and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort.

In this case-cohort study, we examined the association between bulky DNA adducts and the risk of lung cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort with an average 7-year follow-up, including 98 cases of primary lung cancer and 296 subjects randomly selected from the cohort. Aromatic adducts were measured using (32)P-postlabeling in leukocyte DNA from blood samples collected at enrollment. The association between DNA adducts and the risk of lung cancer was estimated using a Cox proportional hazards model with a modified partial likelihood.

Aberrant methylation of hypermethylated-in-cancer-1 and exocyclic DNA adducts in tobacco smokers.

Tobacco smoke has been shown to produce both DNA damage and epigenetic alterations. However, the potential role of DNA damage in generating epigenetic changes is largely underinvestigated in human studies. We examined the effects of smoking on the levels of DNA methylation in genes for tumor protein p53, cyclin-dependent kinase inhibitor2A, hypermethylated-in-cancer-1 (HIC1), interleukin-6, Long Interspersed Nuclear Element type1, and Alu retrotransposons in blood of 177 residents in Thailand using bisulfite-PCR andpyrosequencing.

DNA adducts and combinations of multiple lung cancer at-risk alleles in environmentally exposed and smoking subjects.

Interindividual variation in DNA adduct levels in individuals exposed to similar amounts of environmental carcinogens may be due to genetic variability. We analysed the influence of genes involved in determining/modifying DNA damage, including microsomal epoxide hydrolase1 (EPHX1) His139Arg, N-acetyl-transferase, NAD(P)H:quinone oxidoreductase1 (NQO1) Pro187Ser, manganese superoxide dismutase2 (MnSOD2) Val16Ala, and apurinic/apyrimidinic endonuclease1 (APE1) Asp148Glu polymorphisms in blood of 120 smokers. Subsequently, we examined the effects of the combinations of the variant alleles of EPHX, NQO1 and MnSOD2 together with the wild type allele of APE1 on DNA damage by calculating the "sum of at-risk alleles.

Exocycilic DNA Adducts in a Murine Model of Non-alcoholic Steatohepatitis.

Introduction: Non-alcoholic fatty liver disease is the most common hepatic disorder in Western countries. The transition from abnormal accumulation of lipids toward non-alcoholic steatohepatitis (NASH) represents a key step in the development of chronic liver pathologies. Oxidative stress and lipid peroxidation have often been proposed as mechanisms in the progression to steatohepatitis.