Cytosolic and nuclear progesterone receptors (PRc and PRn) under antiprogestin treatment were measured in rat deciduoma and compared with values for contralateral (nondeciduomatous) rat uterine tissue. Uterine PRc and PRn of the progesterone treated group were 101 +/- 8.7 and 4770 +/- 590 fmol/mg DNA respectively. After treatment with antiprogestins STS-557, 5 alpha-DNE, (5 alpha-dihydronorethisterone), 5 alpha-DNG (5 alpha-dihydronorgestrel), RU-22092 and RU-16556, PRc in the nondeciduomatous control horn ranged from 127 to 377 fmol/mg DNA and PRn from 2785 to 17925 fmol/mg DNA. In the decidual tissue, PRc decreased significantly (4.6 +/- 0.8 fmol/mg DNA) on 5 alpha-DNG treatment as compared with the progesterone alone treatment group (147 +/- 3.8). PRn in decidual tissue also decreased maximally on 5 alpha-DNG treatment. These results suggest that the interaction of antiprogestins may not be identical in control uterine tissue and in deciduoma.
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http://dx.doi.org/10.1016/0022-4731(89)90264-1 | DOI Listing |
Haematologica
November 2021
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen.
Maintenance therapy containing methotrexate and 6-mercapto - purine is essential to cure acute lymphoblastic leukemia (ALL). Cytotoxicity is elicited by incorporation of thioguanine nucleotides into DNA (DNA-TG), and higher leukocyte DNA-TG is associated with increased relapse-free survival. As 6-thioguanine provides 6- fold higher cytosolic levels of thioguanine nucleotides than does 6- mercapto purine, we added low-dose 6-thioguanine to methotrexate/6- mercapto purine maintenance therapy to explore if this combination results in significantly higher DNA-TG.
View Article and Find Full Text PDFInt J Mol Sci
November 2020
Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [H]TH287 to MTH1 was evaluated in live glioblastoma cells (U251MG) through saturation and competitive binding assays, together with in vitro enzymatic assays.
View Article and Find Full Text PDFMutat Res Genet Toxicol Environ Mutagen
January 2020
Department of Environmental Science and Analytical Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden. Electronic address:
The environmental and food contaminant, benzo[a]pyrene {B[a]P, a polycyclic aromatic hydrocarbon (PAH)}, is classified as a human carcinogen by the International Agency for Research on Cancer. The carcinogenicity of B[a]P is linked to the formation of electrophilic metabolites, namely B[a]P-diol epoxides (BPDEs) occurring as stereoisomers. In this work, we quantified the metabolic formation of BPDE isomers and the genotoxic effect in B[a]P-exposed mice, with an aim to estimate the genotoxic potency of B[a]P per in vivo dose of its most potent metabolite [i.
View Article and Find Full Text PDFChem Res Toxicol
April 2019
Masonic Cancer Center , University of Minnesota, Minneapolis , Minnesota 55455 , United States.
The tobacco-specific carcinogens N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) require metabolic activation to exert their carcinogenicity. NNN and NNK are metabolized to the same reactive diazonium ions, which alkylate DNA forming pyridyloxobutyl (POB) DNA base and phosphate adducts. We have characterized the formation of both POB DNA base and phosphate adducts in NNK-treated rats and the formation of POB DNA base adducts in NNN-treated rats.
View Article and Find Full Text PDFMutagenesis
December 2017
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
The tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is metabolically converted to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in a reaction which is both stereoselective and reversible. NNAL is also a lung carcinogen, with both (R)-NNAL and (S)-NNAL inducing a high incidence of lung tumours in rats. Both NNAL and NNK undergo metabolic activation to intermediates which react with DNA to form pyridylhydroxybutyl and pyridyloxobutyl DNA adducts, respectively.
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