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Genotoxic effects induced by combined exposure to beta-carotene and benzo[a]pyrene in ferret lungs
Abstracts / Chemico-Biological Interactions 169 (2007) 132–143
establish the effect of dietary intake of red meat on these levels. Colon biopsies will be taken and analyzed for O6- and N7-methylguanine DNA adducts as markers of NOC-induced genotoxic damage. NOC levels will be determined in blood, urine, and feces to gain insight into the kinetics of NOC in the body. Furthermore, the effect of NOC exposure on multiple gene expression in colon biopsies will be established using a DNA microarray based genomics approach. Up- or down-regulation of specific genes may demonstrate the modulation of genetic pathways, which is an indication of colon cancer development in the long run.
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influence the body weight compared to the control group. The combination of B[a]P and BC resulted in a significant (p < 0.05) increase in body weight compared to BC alone, but not compared to the other groups. The different treatments did not induce enhanced 8-oxodG levels compared with levels in the control group. DNA adduct analysis by 32 P-postlabeling showed no detectable levels in the lungs of the control animals and of BC-treated animals. There was also no influence of BC on DNA adduct levels induced by B[a]P. Our conclusion is that beta-carotene, alone or in combination with benzo[a]pyrene, did not influence our genotoxic parameters.
doi:10.1016/j.cbi.2007.06.010 doi:10.1016/j.cbi.2007.06.011 Genotoxic effects induced by combined exposure to beta-carotene and benzo[a]pyrene in ferret lungs Y.G.J. van Helden a,b , J. Keijer a , R.W.L. Godschalk b , N.L. Franssen-van Hall a , C. Pico c , A. Bunschoten a , A. Palou c , F.J. van Schooten b a
RIKILT–Institute of Food Safety, Food Bioactives Group, Wageningen, The Netherlands b Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands c Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma de Mallorca, Spain Beta-carotene (BC) is a natural food component present in fruit and vegetables. It is widely used as a coloring agent in foods and drinks and as a supplement to correct vitamin A deficiency. Until recently, beta-carotene was considered to be healthy due to its antioxidant properties. However, there is evidence from human intervention trials that a high intake of beta-carotene by cigarette smokers can increase the risk of lung and colon cancer. Our aim was to obtain insight into the mechanism behind the genotoxic effects of beta-carotene in smokers. Therefore, we investigated whether supplementation of ferrets with beta-carotene in combination with exposure to the smoke derived carcinogen benzo[a]pyrene (B[a]P) could influence DNA damage formation in lung tissue. Ferrets (six animals per group) were exposed for 6 months to (1) feed control (2) BC 0.8 mg/kg/day in feed, (3) B[a]P 240 mg/kg by oral gavage three times a week for 10 weeks and (4) B[a]P in combination with BC. Ferrets were chosen because BC metabolism in the ferret resembles the human situation. Markers for DNA damage were measured in the ferret lungs, including B[a]P induced DNA adducts (32 P-postlabeling assay) and 8-oxo-dG (HPLC-ECD). B[a]P treatment did not
Genomics-based biomarkers for genotoxic and immunotoxic risks of newborns exposed to chemicals during pregnancy K. Hochstenbach, D.M. van Leeuwen, J.H.M. van Delft, H. van Loveren Health Risk Analysis and Toxicology (GRAT), Maastricht University, Maastricht, The Netherlands During past decades, there has been an accelerating increase in the incidence of childhood cancers, especially leukemia’s. A worldwide increase is also observed in the prevalence among children of immune diseases, including asthma, allergic rhinoconjunctivitus and atopic eczema/dermatitis. Maternal dietary exposure to genotoxic and/or immunotoxic compounds during pregnancy may represent a risk factor for the development of (childhood) cancers and immune diseases in newborns. Gene expression profiling has recently been shown to be a promising tool for the development of new biomarkers. Therefore, our aim is to develop novel genomics-based biomarkers for genotoxic and immunotoxic risks in newborns. In a developmental phase, modulation of gene expression will be investigated in isolated peripheral blood mononuclear cells (PBMCs), following exposure to a range of food-borne genotoxic and/or immunotoxic chemicals. Using DNA microarrays, transcriptome signatures will be generated which predict carcinogenic and immunotoxic effects of the exposure. For phenotypic anchoring, the obtained genomics profiles will be associated with an established biomarker for carcinogenic effect, namely micronuclei induction, and with cell proliferation as an indicator of immune functionality. Following this development phase, differential gene expression will be investigated in selected mother–child sub-cohorts with known low and high exposures to
establish the effect of dietary intake of red meat on these levels. Colon biopsies will be taken and analyzed for O6- and N7-methylguanine DNA adducts as markers of NOC-induced genotoxic damage. NOC levels will be determined in blood, urine, and feces to gain insight into the kinetics of NOC in the body. Furthermore, the effect of NOC exposure on multiple gene expression in colon biopsies will be established using a DNA microarray based genomics approach. Up- or down-regulation of specific genes may demonstrate the modulation of genetic pathways, which is an indication of colon cancer development in the long run.
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influence the body weight compared to the control group. The combination of B[a]P and BC resulted in a significant (p < 0.05) increase in body weight compared to BC alone, but not compared to the other groups. The different treatments did not induce enhanced 8-oxodG levels compared with levels in the control group. DNA adduct analysis by 32 P-postlabeling showed no detectable levels in the lungs of the control animals and of BC-treated animals. There was also no influence of BC on DNA adduct levels induced by B[a]P. Our conclusion is that beta-carotene, alone or in combination with benzo[a]pyrene, did not influence our genotoxic parameters.
doi:10.1016/j.cbi.2007.06.010 doi:10.1016/j.cbi.2007.06.011 Genotoxic effects induced by combined exposure to beta-carotene and benzo[a]pyrene in ferret lungs Y.G.J. van Helden a,b , J. Keijer a , R.W.L. Godschalk b , N.L. Franssen-van Hall a , C. Pico c , A. Bunschoten a , A. Palou c , F.J. van Schooten b a
RIKILT–Institute of Food Safety, Food Bioactives Group, Wageningen, The Netherlands b Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands c Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma de Mallorca, Spain Beta-carotene (BC) is a natural food component present in fruit and vegetables. It is widely used as a coloring agent in foods and drinks and as a supplement to correct vitamin A deficiency. Until recently, beta-carotene was considered to be healthy due to its antioxidant properties. However, there is evidence from human intervention trials that a high intake of beta-carotene by cigarette smokers can increase the risk of lung and colon cancer. Our aim was to obtain insight into the mechanism behind the genotoxic effects of beta-carotene in smokers. Therefore, we investigated whether supplementation of ferrets with beta-carotene in combination with exposure to the smoke derived carcinogen benzo[a]pyrene (B[a]P) could influence DNA damage formation in lung tissue. Ferrets (six animals per group) were exposed for 6 months to (1) feed control (2) BC 0.8 mg/kg/day in feed, (3) B[a]P 240 mg/kg by oral gavage three times a week for 10 weeks and (4) B[a]P in combination with BC. Ferrets were chosen because BC metabolism in the ferret resembles the human situation. Markers for DNA damage were measured in the ferret lungs, including B[a]P induced DNA adducts (32 P-postlabeling assay) and 8-oxo-dG (HPLC-ECD). B[a]P treatment did not
Genomics-based biomarkers for genotoxic and immunotoxic risks of newborns exposed to chemicals during pregnancy K. Hochstenbach, D.M. van Leeuwen, J.H.M. van Delft, H. van Loveren Health Risk Analysis and Toxicology (GRAT), Maastricht University, Maastricht, The Netherlands During past decades, there has been an accelerating increase in the incidence of childhood cancers, especially leukemia’s. A worldwide increase is also observed in the prevalence among children of immune diseases, including asthma, allergic rhinoconjunctivitus and atopic eczema/dermatitis. Maternal dietary exposure to genotoxic and/or immunotoxic compounds during pregnancy may represent a risk factor for the development of (childhood) cancers and immune diseases in newborns. Gene expression profiling has recently been shown to be a promising tool for the development of new biomarkers. Therefore, our aim is to develop novel genomics-based biomarkers for genotoxic and immunotoxic risks in newborns. In a developmental phase, modulation of gene expression will be investigated in isolated peripheral blood mononuclear cells (PBMCs), following exposure to a range of food-borne genotoxic and/or immunotoxic chemicals. Using DNA microarrays, transcriptome signatures will be generated which predict carcinogenic and immunotoxic effects of the exposure. For phenotypic anchoring, the obtained genomics profiles will be associated with an established biomarker for carcinogenic effect, namely micronuclei induction, and with cell proliferation as an indicator of immune functionality. Following this development phase, differential gene expression will be investigated in selected mother–child sub-cohorts with known low and high exposures to