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Farmer DG

P Costa, J A Simões, S P Alves, J P C Lemos, C M Alfaia, P A Lopes, J A M Prates, J F Hocquette, C R Calkins, V Vleck, R J B Bessa
The traditional beef production in the South of Portugal is based on a discontinuous growth (DG) system that requires lower external inputs and could enhance meat quality and financial returns to cattle producers. This system allows farmers to take advantage of the bull's compensatory growth when the pasture is abundant and finishes the cattle on concentrates for 2 to 3 months before slaughter. The fast gain rate before slaughter could be a valuable strategy to improve tenderness and to reduce its inconsistency in beef production...
January 2017: Animal: An International Journal of Animal Bioscience
Emelie A C Westberg, Rajinder Singh, Ulla Hedebrant, Georgios Koukouves, Vassilis L Souliotis, Peter B Farmer, Dan Segerbäck, Soterios Kyrtopoulos, Margareta Å Törnqvist
Stable and specific biomacromolecular adducts can be used to measure in vivo doses of reactive compounds. An LC/MS-MS method to measure adducts from the benzo[a]pyrene (BP) metabolite (±)-anti-BP-7,8-diol-9,10-epoxide ((±)-anti-BPDE) to His(146) in serum albumin (SA), earlier evaluated on in vitro alkylated human SA, was tested for its applicability to mouse. It was shown that (+)-anti-BPDE form BPDE-His adducts to mouse SA. The method was applied to samples from BP-exposed mice (100mg/kg of body weight for 1, 3, 7 and 28 days)...
January 5, 2015: Toxicology Letters
Rajinder Singh, Jolanta Gromadzinska, Yogita Mistry, Rebecca Cordell, Tina Juren, Dan Segerbäck, Peter B Farmer
Epidemiological studies have shown an association between alcohol (ethanol) consumption and increased cancer risk. The effect of alcohol consumption on the levels and persistence of N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) formed by acetaldehyde, the oxidative metabolite of ethanol, in human leukocyte DNA was investigated. DNA was isolated from venous blood samples obtained from 30 male non-smoking individuals before consumption of alcohol (0h) and subsequently at 3-5h following the consumption of 150mL of vodka (containing 42% pure ethanol)...
September 1, 2012: Mutation Research
Volker M Arlt, Rajinder Singh, Marie Stiborová, Gonçalo Gamboa da Costa, Eva Frei, James D Evans, Peter B Farmer, C Roland Wolf, Colin J Henderson, David H Phillips
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking of foods, induces colon cancer in rodents. PhIP is metabolically activated by cytochromes P450 (P450s). To evaluate the role of hepatic P450s in the bioactivation of PhIP, we used Reductase Conditional Null (RCN) mice, in which cytochrome P450 oxidoreductase (POR), the unique electron donor to P450s, can be specifically deleted in hepatocytes by pretreatment with 3-methylcholanthrene (3-MC), resulting in the loss of essentially all hepatic P450 function...
December 2011: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rajinder Singh, Volker M Arlt, Colin J Henderson, David H Phillips, Peter B Farmer, Gonçalo Gamboa da Costa
The heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed by the grilled cooking of certain foods such as meats, poultry and fish. PhIP has been shown to induce tumours in the colon, prostate and mammary glands of rats and is regarded as a potential human dietary carcinogen. PhIP is metabolically activated via cytochrome P450 mediated oxidation to an N-hydroxylamino-PhIP intermediate that is subsequently converted to an ester by N-acetyltransferases or sulfotransferases and undergoes heterolytic cleavage to produce a PhIP-nitrenium ion, which reacts with DNA to form the N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP-C8-dG) adduct...
August 1, 2010: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Ann-Karin Olsen, Ashild Andreassen, Rajinder Singh, Richard Wiger, Nur Duale, Peter B Farmer, Gunnar Brunborg
BACKGROUND: Spermatozoal DNA damage is associated with poor sperm quality, disturbed embryonic development and early embryonic loss, and some genetic diseases originate from paternal de novo mutations. We previously reported poor repair of bulky DNA-lesions in rodent testicular cells. METHODOLOGY/PRINCIPAL FINDINGS: We studied the fate of DNA lesions in the male germ line. B[a]PDE-N(2)-dG adducts were determined by liquid chromatography-tandem mass spectrometry, and de novo mutations were measured in the cII-transgene, in Big Blue mice exposed to benzo[a]pyrene (B[a]P; 3 x 50 mg/kg bw, i...
2010: PloS One
Gonçalo Gamboa da Costa, Rajinder Singh, Volker M Arlt, Amin Mirza, Meirion Richards, Takeji Takamura-Enya, Heinz H Schmeiser, Peter B Farmer, David H Phillips
The aromatic nitroketone 3-nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one; 3-NBA) is an extremely potent mutagen and a suspected human carcinogen detected in the exhaust of diesel engines and in airborne particulate matter. 3-NBA is metabolically activated via reduction of the nitro group to the hydroxylamine (N-OH-3-ABA) to form covalent DNA adducts. Thus far, the detection and quantification of covalent 3-NBA-DNA adducts has relied solely on (32)P-postlabeling methodologies. In order to expand the range of available techniques for the detection and improved quantification of 3-NBA-DNA adducts, we have developed a method based upon online column-switching HPLC coupled to electrospray tandem mass spectrometry, with isotopic dilution of (15)N-labeled internal standards...
November 2009: Chemical Research in Toxicology
Rajinder Singh, Jatinderpal Sandhu, Balvinder Kaur, Tina Juren, William P Steward, Dan Segerbäck, Peter B Farmer
Acetaldehyde is an ubiquitous genotoxic compound that has been classified as a possible carcinogen to humans. It can react with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct. An online column-switching valve liquid chromatography tandem mass spectrometry (LC-MS/MS) selected reaction monitoring (SRM) method was developed for the determination of N(2)-ethylidene-dG adducts in DNA following reduction with sodium cyanoborohydride (NaBH(3)CN) to the chemically stable N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) adduct...
June 2009: Chemical Research in Toxicology
Evagelos Liapis, Keith I E McLuckie, Paul D Lewis, Peter B Farmer, Karen Brown
Tamoxifen elevates the risk of endometrial tumours in women and alpha-(N(2)-deoxyguanosinyl)-tamoxifen adducts are reportedly present in endometrial tissue of patients undergoing therapy. Given the widespread use of tamoxifen there is considerable interest in elucidating the mechanisms underlying treatment-associated cancer. Using a combined experimental and multivariate statistical approach we have examined the mutagenicity and potential consequences of adduct formation by reactive intermediates in target uterine cells...
October 2008: Nucleic Acids Research
Sanjeev Pathak, Rajinder Singh, Richard D Verschoyle, Peter Greaves, Peter B Farmer, William P Steward, J Kilian Mellon, Andreas J Gescher, Ricky A Sharma
Intracellular reactive oxygen species (ROS) may cause oxidative DNA damage, resulting in the formation of adducts such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and the cyclic pyrimidopurinone N-1, N(2) malondialdehyde-2'-deoxyguanosine (M(1)dG). These adducts have been associated with carcinogenesis, genomic instability and clonal evolution. We tested two hypotheses in human prostate cancer cells grown in vitro and in a xenograft model: (1) treatment of androgen-sensitive cells with DHT increases levels of oxidative DNA adduct levels; (2) flutamide, a competitive androgen receptor antagonist, prevents DHT-induced changes...
March 8, 2008: Cancer Letters
Karen Brown, Elaine M Tompkins, David J Boocock, Elizabeth A Martin, Peter B Farmer, Kenneth W Turteltaub, Esther Ubick, David Hemingway, Emma Horner-Glister, Ian N H White
Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the United States for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women, and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated, but much interest has focused on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to 10 women as a single [(14)C]-labeled therapeutic (20 mg) dose, approximately 18 h before undergoing colon resections...
July 15, 2007: Cancer Research
Rajinder Singh, Radim J Sram, Blanka Binkova, Ivan Kalina, Todor A Popov, Tzveta Georgieva, Seymour Garte, Emanuela Taioli, Peter B Farmer
Polycyclic aromatic hydrocarbons (PAHs) appear to be significant contributors to the genotoxicity and carcinogenicity of air pollution present in the urban environment for humans. Populations exposed to environmental air pollution show increased levels of PAH DNA adducts and it has been postulated that another contributing cause of carcinogenicity by environmental air pollution may be the production of reactive oxygen species following oxidative stress leading to oxidative DNA damage. The antioxidant status as well as the genetic profile of an individual should in theory govern the amount of protection afforded against the deleterious effects associated with exposure to environmental air pollution...
July 1, 2007: Mutation Research
Rajinder Singh, Balvinder Kaur, Ivan Kalina, Todor A Popov, Tzveta Georgieva, Seymour Garte, Blanka Binkova, Radim J Sram, Emanuela Taioli, Peter B Farmer
Epidemiological studies conducted in metropolitan areas have demonstrated that exposure to environmental air pollution is associated with increases in mortality. Carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) are the major source of genotoxic activities of organic mixtures associated with respirable particulate matter, which is a constituent of environmental air pollution. In this study,we wanted to evaluate the relationship between exposure to these genotoxic compounds present in the air and endogenous oxidative DNA damage in three different human populations exposed to varying levels of environmental air pollution...
July 1, 2007: Mutation Research
Seymour Garte, Emanuela Taioli, Sara Raimondi, Valentina Paracchini, Blanka Binkova, Radim J Sram, Ivan Kalina, Todor A Popov, Rajinder Singh, Peter B Farmer
Data from the EXPAH project on PAH exposure and intermediary biomarkers were analyzed with respect to individual genotypes at seven metabolic gene loci. The GSTM1 null allele was associated with significantly higher levels of two biomarkers, malondialdehyde-2'-deoxyguanosine and benzo[a]pyrene DNA adducts in the total population from three Central and Eastern European countries. The CYP1B1 Leu/Val variant demonstrated effects on both markers of oxidative DNA damage in opposite directions, producing a higher level of M(1)dG with a trend from wild type (Leu/Leu) to heterozygotes to homozygous (Val/Val) variants, whereas the effects of these variants were reversed for 8-oxodG...
July 1, 2007: Mutation Research
Rajinder Singh, Margaret Gaskell, Rachel C Le Pla, Balvinder Kaur, Ali Azim-Araghi, Jonathan Roach, George Koukouves, Vassilis L Souliotis, Soterios A Kyrtopoulos, Peter B Farmer
The polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P) is a proven animal carcinogen that is potentially carcinogenic to humans. B[a]P is an ubiquitous environmental pollutant and is also present in tobacco smoke, coal tar, automobile exhaust emissions, and charred food. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using electrospray ionization and selected reaction monitoring (SRM) has been developed for the detection of 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE-N(2)dG) adducts formed in DNA following the metabolic activation of B[a]P to benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (B[a]PDE)...
June 2006: Chemical Research in Toxicology
Rachel C Le Pla, Karen J Bowman, Peter B Farmer, George D D Jones
DNA phosphate oxygens are sites for alkylation leading to DNA phosphotriester adduct (PTE) formation. Previously, we have reported that the manifestation of PTEs was nonrandom in mouse liver DNA treated in vivo [Guichard et al. (2000) Cancer Res. 60, 1276-1282], and while further studies revealed possible PTE repair, this was determined not to play a role in the observed nonrandom manifestation in vivo [Le Pla et al. (2004) Chem. Res. Toxicol. 17, 1491-1500]. In the present study, to determine whether the nonrandom manifestation of PTEs in vivo was specifically due to their nonrandom formation, we have compared the in vitro formation of diethylsulfate (DES)-induced PTEs in h2E1/OR human B-lymphoblastoid cells, their isolated nuclei, and their isolated DNA, using the 5' nearest neighbor analysis postlabeling procedure developed by Le Pla et al...
March 2006: Chemical Research in Toxicology
R G Tunstall, R A Sharma, S Perkins, S Sale, R Singh, P B Farmer, W P Steward, A J Gescher
The natural polphenol, curcumin, retards the growth of intestinal adenomas in the Apc(Min+) mouse model of human familial adenomatous polyposis. In other preclinical models, curcumin downregulates the transcription of the enzyme cyclooxygenase-2 (COX-2) and decreases levels of two oxidative DNA adducts, the pyrimidopurinone adduct of deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). We have studied COX-2 protein expression and oxidative DNA adduct levels in intestinal adenoma tissue from Apc(Min+) mice to try and differentiate between curcumin's direct pharmacodynamic effects and indirect effects via its inhibition of adenoma growth...
February 2006: European Journal of Cancer
Keith I E McLuckie, Robert J R Crookston, Margaret Gaskell, Peter B Farmer, Michael N Routledge, Elizabeth A Martin, Karen Brown
Tamoxifen, a breast cancer drug, has recently been approved for the chemoprevention of this disease. However, tamoxifen causes hepatic carcinomas in rats through a genotoxic mechanism and increases the risk of endometrial tumors in women. DNA adducts have been detected at low levels in human endometrium, and there is much interest in determining whether DNA damage plays a role in tamoxifen-induced endometrial carcinogenesis. This study investigates the mutagenicity of tamoxifen DNA adducts formed by alpha-acetoxytamoxifen, a reactive ester producing the major DNA adduct formed in livers of tamoxifen-treated rats...
June 7, 2005: Biochemistry
J Farmer, X Zhao, H van Praag, K Wodtke, F H Gage, B R Christie
We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise...
2004: Neuroscience
Rajinder Singh, Michael McEwan, John H Lamb, Regina M Santella, Peter B Farmer
The analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) represents an important biomarker of oxidative stress. A sensitive method for the detection of 8-oxodG in DNA samples has been developed that utilizes immunoaffinity column purification of 8-oxodG followed by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) multiple reaction monitoring (MRM) mode analysis. An internal standard of stable-isotopically labelled 8-oxodG containing [(15)N(5)] was added prior to the enzymatic digestion of DNA to deoxynucleosides, which was then subjected to immunoaffinity column purification followed by microbore positive ion LC/MS/MS MRM...
2003: Rapid Communications in Mass Spectrometry: RCM
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