Cytogenetic characterizations were made of lymphocyte colonies established from somatic mutation assays for 6-thioguanine (TG) resistance in Hiroshima atomic bomb survivors. G-banded chromosomes were analyzed in both TG-resistant (TGr) and wild-type colonies. Included were 45 TGr and 19 wild-type colonies derived from proximally exposed A-bomb survivors, as well as colonies from distally exposed control individuals who did not receive a significant amount of A-bomb radiation (18 TGr and 9-wild type colonies). Various structural and numerical chromosome abnormalities were observed in both TGr and wild-type colonies. Aberrations of the X chromosome, on which the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus is present, were found in 6 colonies: 2 resistant colonies from controls (45,X/46,XX; 46,X,ins(X)), 3 resistant colonies (45,X/46,XX/46,X, + mar; 46,X,t(Xq +;14q-); 46,Y,t(Xq-;5q +)), and 1 wild-type colony (45,X/47,XXX) from proximally exposed persons. In cases with exchange aberrations, each of the break points on the X chromosome was situated proximally to band q26 where the HPRT locus is known to be assigned. DNA-replicating patterns were also studied, and it was found that abnormal X chromosomes showed early replicating patterns, while normal X chromosomes showed late replicating patterns.
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http://dx.doi.org/10.1016/0165-7992(89)90065-1 | DOI Listing |
Environ Mol Mutagen
July 2024
Pfizer Research, Development, and Medical, Groton, Connecticut, USA.
The detection of N-nitrosamines in drug products has raised global regulatory interest in recent years due to the carcinogenic potential of some nitrosamines in animals and a need to identify a testing strategy has emerged. Ideally, methods used would allow for the use of quantitative analysis of dose-response data from in vivo genotoxicity assays to determine a compound-specific acceptable intake for novel nitrosamines without sufficient carcinogenicity data. In a previous study we compared the dose-response relationships of N-nitrosodiethylamine (NDEA) in three in vivo genotoxicity endpoints in rats.
View Article and Find Full Text PDFBiochemistry
May 2023
Department of Chemistry and Biochemistry, Loyola University Chicago, 1068 West Sheridan Road, Chicago, Illinois 60660, United States.
Thioredoxin/glutathione reductase from (SmTGR) catalyzes the reduction of both oxidized thioredoxin and glutathione with electrons from reduced nicotinamide adenine dinucleotide phosphate (NADPH). SmTGR is a drug target for the treatment of Schistosomiasis, an infection caused by platyhelminths residing in the blood vessels of the host. spp.
View Article and Find Full Text PDFActa Pharm Sin B
February 2022
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA.
Pharmacological activation of the xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is well-known to increase drug metabolism and reduce inflammation. Little is known regarding their physiological functions on the gut microbiome. In this study, we discovered bivalent hormetic functions of PXR/CAR modulating the richness of the gut microbiome using genetically engineered mice.
View Article and Find Full Text PDFOxid Med Cell Longev
November 2021
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.
Objective: The aim of the present study was to investigate the protective effects and mechanisms of KLK1 on aging-related prostate alterations and search clues about the application of KLK1 to the treatment of human BPH.
Methods: Thirty-six rats including 26 male wild-type SD rats and 10 transgenic rats were fed to 3- or 18-month-old and divided into three groups: young WTR (yWTR) as the control ( = 16), aged WTR (aWTR) ( = 10), and aged TGR (aTGR) ( = 10). The prostates of the three groups of rats (10 rats per group) were harvested to evaluate the levels of KLK1 expression, oxidative stress, fibrosis, and involved signaling pathways, such as NO/cGMP, COX-2/PTGIS/cAMP, and TGF-1/RhoA/ROCK1, via quantitative PCR, Western blot, histological examinations, and ELISA.
Parasit Vectors
April 2021
School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, 621010, China.
Background: Schistosomiasis is a chronic parasitic disease that affects millions of people's health worldwide. Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR).
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