Rapid screening assay for mutagen sensitivity and DNA repair capacity in human peripheral blood lymphocytes

Schmezer, Peter; Rajaee-Behbahani, Nahid; Risch, Angela; Thiel, S; Rittgen, Werner; Drings, P.; Dienemann, Hendrik; Kayser, Klaus; Schulz, Viktor; Bartsch, Helmut

doi:10.1093/mutage/16.1.25

Cited by 103 publications

(74 citation statements)

References 24 publications

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“…Several case-control studies in which bleomycininduced DNA damage was measured indicate that cancer patients have reduced DNA repair capacity. 21,22 Furthermore, PARP activity has been observed after bleomycin-induced DNA damage in phytohemagglutinin-stimulated human peripheral blood lymphocytes. 23 Here, we report on the development of a quantitative immunofluorescence assay for measuring PARP activity, which includes a specific monoclonal antibody (MAb) and computerized image analysis.…”

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confidence: 99%

Reduced poly(ADP‐ribosyl)ation in lymphocytes of laryngeal cancer patients: Results of a case‐control study

Rajaee-Behbahani

Schmezer

Ramroth

et al. 2002

Intl Journal of Cancer

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Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that is catalytically activated by DNA strand breaks, plays a complex role in DNA repair. Using NAD ؉ as a precursor, it catalyzes the formation of ADP-ribose polymers, which are attached to various proteins. Defects in DNA repair pathways have been associated with increased risks for cancer in humans. We investigated whether differences in the activity of PARP are associated with the risk for laryngeal cancer. In a case-control study on genetic, lifestyle and occupational risk factors for laryngeal cancer, PARP activity was assessed as DNA damage-induced poly(ADP-ribose) formation in human peripheral blood lymphocytes by quantitative immunofluorescence analysis. Polymer formation was determined as the cellular response to bleomycin, a well-known inducer of DNA strand breaks, in lymphocytes from 69 laryngeal cancer patients and 125 healthy controls. The frequency of bleomycin-induced polymer formation, measured as mean pixel intensity, was significantly lower in cases (74.6, SE ‫؍‬ 3.7) than in controls (94.5, SE ‫؍‬ 3.5) and not influenced by smoking, age or sex. There was no significant difference between cases (59.1, SE ‫؍‬ 5.2) and controls (50.5, SE ‫؍‬ 3.7) in basal polymer formation (in cells not treated with bleomycin). When the highest tertile of polymer formation was used as the reference, the odds ratio for the lowest tertile of bleomycininduced polymer formation was 3.79 (95% confidence interval 1.37-10.47, p ‫؍‬ 0.01). Peripheral blood lymphocytes from laryngeal cancer patients thus showed significantly less bleomycin-induced poly(ADP-ribose) formation. 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. © 2002 Wiley-Liss, Inc. Key words: biomarker; bleomycin; molecular epidemiology; laryngeal cancer; poly(ADP-ribose) polymeraseLaryngeal carcinoma is the commonest tumor of the head and neck and the second commonest respiratory tract cancer after lung cancer in white persons. Respiratory cancers are paradigms of environmentally induced diseases and epidemiologic studies have identified smoking and alcohol intake as the most important risk factors. Other risk factors (poor nutrition, exposure to asbestos and other occupational exposures) have also been associated in some studies with the risk for laryngeal cancer. 1-3 These risk factors alone cannot, however, completely explain all cases of this cancer. Many studies have been conducted to identify biomarkers that reflect host susceptibility more closely. Those that have been found include variations in carcinogen metabolism, DNA adduct formation and DNA repair activity. 4,5 The pathogenic implications of these markers have been established for environmentally induced cancers such as lung tumors and head-and-neck squamous cell carcinoma. 6,7 An important reaction in DNA repair pathways is poly(ADP-ribosyl)ation, which is induced by the presence ...

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confidence: 99%

Reduced poly(ADP‐ribosyl)ation in lymphocytes of laryngeal cancer patients: Results of a case‐control study

Rajaee-Behbahani

Schmezer

Ramroth

et al. 2002

Intl Journal of Cancer

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“…The Wilcoxon rank-sum test was used to determine the statistical significance of the case-control comparisons of DRC (Schmezer et al, 2001). The impact factors for DRC were evaluated by linear stepwise regression.…”

Section: Discussionmentioning

confidence: 99%

“…Lower DRC is associated with higher mutagen sensitivity (Schmezer et al, 2001). For these reasons, DRC has been recommended as a molecular epidemiological marker for cancer research.…”

Section: Discussionmentioning

confidence: 99%

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DNA Repair Capacity, DNA-Strand Break Repair Gene Polymorphisms, and the Incidence of Hepatocellular Carcinoma in Southwestern Guangxi of China

Zeng

Liu

et al. 2012

DNA and Cell Biology

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The associations between DNA repair capacity (DRC), DNA repair gene polymorphisms, and the incidence of hepatocellular carcinoma (HCC) have not been determined in high-risk areas. The aims of this study were to investigate whether DRC is related to the incidence of HCC and to determine whether polymorphisms in the DNA repair genes that regulate DRC are associated with the risk of HCC. First, a small case-control study was conducted to examine the association between DRC and the incidence of HCC and the environmental and genetic factors regulating DRC. Then, a large case-control study was conducted to determine whether those DNA repair gene polymorphisms shown to regulate DRC were related to the risk of HCC. The median DRC was significantly lower among the cases (0.80) than the controls (0.93). A multivariate linear regression analysis showed that the HBsAg status ( p < 0.01), ethnicity ( p = 0.01), and polymorphisms in the XRCC3-241 ( p = 0.01) and APE1-148 ( p = 0.03) gene loci may be impact factors for DRC. In the large case-control study, a stratified analysis showed that individuals with the APE1-148-combined genotype GT + TT likely had a significantly higher HCC risk compared with those with only the GG genotype (crude odds ratio = 1.93, 95% confidence interval = 1.17-3.17) among the Zhuang ethnicity. However, nonsignificant differences were observed between XRCC3-241 polymorphisms and the HCC risk. DRC may be related to the incidence of HCC as determined by environmental and genetic factors found in southwestern part of the Guangxi Province. Gene-environment interactions play an important role in the incidence and progression of HCC.

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“…These cryopreserved PBMC are suitable and accepted biomarkers, e.g. to analyse effects of intrinsic and extrinsic factors on oxidative DNA damage [30,39]. Since modulation of gene expression was the endpoint in this study, we investigated how storage and the mitotic stimulation affect the responsiveness of these cells.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles in human peripheral blood mononuclear cells as biomarkers for nutritional in vitro and in vivo investigations

et al. 2010

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Identification of chemopreventive substances may be achieved by measuring biological endpoints in human cells in vitro. Since generally only tumour cells are available for such investigations, our aim was to test the applicability of peripheral blood mononuclear cells (PBMC) as an in vitro primary cell model since they mimic the human in vivo situation and are relatively easily available. Cell culture conditions were refined, and the basal variation of gene expression related to drug metabolism and stress response was determined. Results were compared with profiles of an established human colon cell line (HT29) as standard. For biomarker development of nutritional effects, PBMC and HT29 cells were treated with potentially chemopreventive substances (chrysin and butyrate), and gene expression was determined. Key results were that relevant stress response genes, such as glutathione S-transferase T2 (GSTT2) and GSTM2, were modulated by butyrate in PBMC as in HT29 cells, but the blood cells were less sensitive and responded with high individual differences. We conclude that these cells may serve as a surrogate tissue in dietary investigations and the identified differentially expressed genes have the potential to become marker genes for population studies on biological effects.

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Rapid screening assay for mutagen sensitivity and DNA repair capacity in human peripheral blood lymphocytes

Cited by 103 publications

References 24 publications

Reduced poly(ADP‐ribosyl)ation in lymphocytes of laryngeal cancer patients: Results of a case‐control study

Reduced poly(ADP‐ribosyl)ation in lymphocytes of laryngeal cancer patients: Results of a case‐control study

DNA Repair Capacity, DNA-Strand Break Repair Gene Polymorphisms, and the Incidence of Hepatocellular Carcinoma in Southwestern Guangxi of China

Gene expression profiles in human peripheral blood mononuclear cells as biomarkers for nutritional in vitro and in vivo investigations

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