Helmut Bartsch

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..If so, the efficacy of human chemopreventive interventions for malignant disease prevention could be verified...

..Etheno-DNA adducts are thus promising markers to verify the efficiency of chemopreventive measures in humans...

..Mechanisms and host-factors that influence the steady-state levels of epsilon-DNA adducts in cancer prone tissues are under investigation...

..Steady-state levels of LPO-derived (etheno-) DNA adducts in organs affected by persistent inflammatory processes were investigated as potential lead markers for assessing progression of inflammatory cancer-prone diseases...

..g. [Lancet Oncol. 1 (2000) 107]) and chemopreventive agents in lowering oxidative stress and related cancer risk...

..The underlying mechanisms as to why AA homozygotes are predisposed to lung adenocarcinoma and which specific carcinogens are involved remains to be determined...

..To confirm these observations and to eliminate possible bias in our analyses, larger studies are warranted...

..We conclude that promutagenic LPO-derived DNA lesions are involved in the onset of hepatocellular carcinoma in these patients...

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..To confirm our observation that the CYP3A4*1B allele increases SCLC risk and modifies the smoking-related lung cancer risk in a gender-specific manner, further studies, including CYP3A haplotype analysis, will be necessary...

..As part of the Rhein-Neckar Larynx-case-control study, this study investigated the potential risk-modifying effect of genetic polymorphisms in enzymes involved in ethanol and tobacco carcinogen metabolism for laryngeal cancer in Germany...

..Our study further revealed a modulating effect by nutritional factors...

..Similar studies in human breast epithelial tissue and on amplification of DNA-damage in breast cancer patients are in progress...

..Analyses of additional DNA repair gene interactions in larger population-based studies are warranted for identification of high-risk subjects...

..The predictive value of DNA damage-induced XPC levels as a possible biomarker for radiosensitivity has to be further investigated...

..Nevertheless, confirmation by further molecular and epidemiological studies is warranted...

..The described methods are useful in diagnosis and monitoring of chronic degenerative diseases, including cancer, atherosclerosis, and neurodegenerative disorders...

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..63 and P = 0.42 for CYP1B1 and CYP2A13, respectively). Our results suggest that the CYP1B1 and the CYP2A13 genotypes may contribute to individual susceptibility to early-onset lung cancer in women...

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..Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status...

..Exocyclic etheno-DNA adducts, which are formed by LPO-products such as 4-hydroxy -2-nonenal, are strongly pro-mutagenic DNA lesions...

..Although these data suggest no role for increased LPO derived DNA damage in the onset of atherogenesis in ApoE-KO mice, the potentially modulating role of Ape1/Ref1 in the arterial wall deserves further attention...

..LPO-induced adduct formation in nuclear and mitochondrial DNA appear as early lesions in LEC rat liver carcinogenesis and are discussed in relation to apoptotic events in the progression of malignant disease...

..These novel antiangiogenic activities of sulforaphane are likely to contribute to its cancer chemopreventive and therapeutic potential...

..The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy...

..Colon was a target for LPO-derived DNA-adducts in both LA-treated male and female rats, supporting their role in omega-6 PUFA induced colon carcinogenesis...

..Depletion of GSH does not seem to play a role in SFN-mediated apoptosis induction. Our data clearly contribute to a better understanding of the kinetics of antiproliferative activity of SFN...

..04-2.47; n = 256). In conclusion, this study prioritizes ABCC3 C-211T and ABCG2 C421A as candidate transporter SNPs to be further investigated as possible predictors of the clinical outcome of chemotherapy in lung cancer patients...

..Future strategies in molecular cancer epidemiology for identifying such susceptible individuals are discussed with emphasis on well-designed larger studies...

..Constitutive mRNA expression of repair genes was investigated in such patients to analyze whether expression patterns are predictive for therapy-related acute side effects...

..The European Commission held a major conference from 11 to 13 November 2002 in the Palais du Heysel in Brussels to mark the launch of the European Union's Sixth Framework Programme (FP-6) for research, which covers the period 2002-2006...

..Such a marker might help optimize lung cancer treatment in a tailored approach...

..This study further indicates that etheno-DNA adducts are useful biomarkers for in vivo oxidative stress in atherosclerosis...

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..These data stress the need for elucidating mechanistic interactions for better predicting beneficial health effects of bioactive food components...

..These highly promutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma...

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..Before translating these findings into clinical use and application for public health measures, large population-based studies and validation of the results will be required...

..In conclusion, gene expression profiles induced by compounds that act via similar mechanisms showed common effects on transcription upon treatment in vivo and in rat liver slices in vitro...

..Our data demonstrate for the first time an induction of CYP2E1 in the esophageal mucosa by ethanol in a dose dependent manner in man and may explain, at least in part, the generation of carcinogenic DNA lesions in this target organ...

..Our results demonstrate increased LPO-induced DNA damage in organs of OXYS rats which correlates with their known shorter life-span and elevated frequency of chronic degenerative diseases...

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..This pilot study also indicated a protective effect of dietary vitamin E and vegetables against miscoding, lipid peroxidation-induced DNA lesions...

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..These data clearly show the importance of separating different histological lung tumour subtypes in studies on genetic susceptibility factors and implicate the NAT1*10 allele as a risk factor for adenocarcinoma...

..Further, education to reduce or eliminate home-made preparations needs to be accelerated...

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..As epsilon-DNA adducts are biomarkers for oxidative stress and LPO induced DNA damage, they can verify the efficacy of newly identified antioxidants, e.g. from olive oil, as chemopreventive agents against colon carcinogenesis...

..The modified method described is less complex, amenable to use with commercially available SPE columns and fulfils all the reliability criteria, resulting in highly specific and accurate results...

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..Overall the workshop aimed at raising awareness among European clinical and laboratory researchers of the importance of the development of novel, efficacious and safe cancer preventive agents...

..We conclude that curcumin should be contra-indicated for patients suffering from inherited and acquired metal storage diseases that include patients with hepatitis C virus infection...

..This ultrasensitive detection method is thus suitable for applications in human biomonitoring and molecular epidemiology studies...

..In cancer-prone liver diseases (fatty liver, cirrhosis/fibrosis) such damage may act as a driving force towards malignancy...

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..By inactivation of proteolytic enzymes they inhibit the development of metastases. This short review summarizes relevant recent findings on the protective effects of green tea constituents...

..Prospective cohort studies have to reveal whether these two WBC-DNA adducts could serve as risk indicator for developing hematopoietic cancers and other disorders later in life...

..Therefore, exocyclic DNA adducts offer new tools in cancer aetiological research and in verifying the efficacy of chemopreventive agents...

..The latter role for GSTT1 would explain the observed lower risk of SCC and hamartoma associated with GSTT1 null. Further confirmatory studies are required...

..The conclusion is that promutagenic etheno-DNA adducts are generated as a consequence of chronic inflammation, acting as a driving force to malignancy in cancer-prone inflammatory diseases...

..Overall, our data indicate that inhibition of endothelial cell function contributes to various extents to the chemopreventive or anti-angiogenic potential of these lead compounds...

..We confirm that the MPO -463 A variant affords a protective effect against lung cancer risk in smokers, which was strongest for SCLC patients...

..Validation of this assay in large prospective studies for the identification of subjects at high risk for non-small cell lung cancer is now warranted...

..49+/-1.76 (SD) fmol micromol-1 creatinine (range 0.66-6.42). By this non-invasive method, epsilondC in human urine could be explored as a biomarker for oxidative stress-related human diseases...

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..Together, our data provide evidence for the potential application of XN as a novel, readily available chemopreventive agent, and clinical investigations are warranted once efficacy and safety in animal models have been established...

..Our improved assay was found to be sufficiently sensitive and specific to detect O(4)-etT in surrogate cells from cigarette smoke exposed humans...

..Kampo-derived natural products represent a valuable reservoir for individual tumour treatment strategies in the future...

..The possible interaction of chemopreventive agents with metabolic polymorphisms as biomarkers in chemoprevention trials is discussed...

..Advances in the application of selected biomarkers in human studies are reviewed and illustrated by examples from the author's research conducted during the past two decades...

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..e., adduct formation (preferably at specific sites), mutational spectra in cancer-relevant genes, and genetic markers of (cancer) susceptibility in a number of cancer-predisposing genes...

..Thus, the etheno adducts are implicated as initiating DNA damage in copper/iron-induced carcinogenesis in humans and should also be explored as biomarkers in disease progression and prevention trials...

..Our results suggest that a reduced capacity of somatic cells to synthesize poly(ADP-ribose) might be associated with an increased risk for laryngeal cancer. The underlying mechanism remains to be investigated...

..The new method should enable large epidemiologic, case-control and intervention studies on the relevance of phenolic antioxidants in the aetiology of colorectal cancer to be conducted in the future...

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..In conclusion, these data show for the first time: (i) the in vivo formation of BPDE-DNA adducts in human skin treated with coal tar; (ii) that the MPO-463AA/AG genotype reduced BPDE-DNA adduct levels in human skin...

..A possible association between these biomarkers, particularly in relation to dietary fat intake and antioxidant status, should now be studied in a larger trial...

..P53-specific laboratory models, combined with DNA microchips designed for high through-put mutation screening promise to unmask information currently hidden in the compilation of human tumor p53 mutations...

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..Our data provide novel evidence that anti-inflammatory mechanisms contribute to sulforaphane-mediated cancer chemoprevention...

..It seems probable that olive and olive oil consumption in southern Europe represents an important contribution to the beneficial effects on health of the Mediterranean diet...

..In conclusion, lymphocyte DNA from female patients treated at therapeutic levels did not show evidence of the formation of TAM- or TOR-DNA adducts...

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..51, n = 27, P = 0.02). Our results demonstrate that the short-term fasting reduces lipid peroxidation products but does not affect oxidative stress-induced DNA damage...

..Their use in risk-assessment, however, requires further investigation...

..08). Results from this pilot study suggest urinary epsilon dA as a potential biomarker of DNA damage possibly derived from salt-induced inflammation and LPO; further exploration of epsilon dA in human biomonitoring studies is warranted...

..These findings suggested a critical function for G6PD in limiting oxidative mutagenesis in the mouse brain...

..48, 95% CI 0.82-2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry...

..26-2.82). In conclusion, our data suggest that Thai women with a certain XRCC1 diplotype or homozygous for two or three variant alleles of XRCC1, OGG1, and APEX1 are likely to have an increased susceptibility to breast cancer...