Benzene ; DNA Damage ; Humans ; Research

Animals ; DNA Damage ; DNA Repair ; DNA, Neoplasm ; Humans

Animals ; DNA Damage ; DNA Repair ; DNA-Activated Protein Kinase ; Humans

53BP1 is an important genome stability regulator, which protects cells against double-strand breaks. Following DNA damage, 53BP1 is rapidly recruited to sites of DNA breakage, along with other DNA damage response proteins, including gamma-H2AX, MDC1, and BRCA1. The recruitment of 53BP1 requires a tandem Tudor fold which associates with methylated histones H3 and H4. It has already been determined that the majority of DNA damage response proteins are phosphorylated by ATM and/or ATR after DNA damage, and then recruited to the break sites. 53BP1 is also phosphorylated at several sites, like other proteins after DNA damage, but this phosphorylation is not critically relevant to recruitment or repair processes. In this study, we evaluated the functions of phosphor-53BP1 and the role of the BRCT domain of 53BP1 in DNA repair. From our data, we were able to detect differences in the phosphorylation patterns in Ser25 and Ser1778 of 53BP1 after neocarzinostatin-induced DNA damage. Furthermore, the foci formation patterns in both phosphorylation sites of 53BP1 also evidenced sizeable differences following DNA damage. From our results, we concluded that each phosphoryaltion site of 53BP1 performs different roles, and Ser1778 is more important than Ser25 in the process of DNA repair.
DNA ; DNA Damage ; DNA Repair ; Genomic Instability ; Histones ; Phosphorylation ; Proteins

DNA ; DNA Damage ; DNA Repair ; Fanconi Anemia/genetics* ; Humans

OBJECTIVES: To investigate the possibility of utilizing DNA adduct as a carcinogenic biological marker for workers exposed to chromium, and the effect of chromium exposure on the formation of urinary 8-hydroxydeoxyguanosine(8-OH-dG) was also evaluated. METHODS: The chromium concentrations of venous blood and urine were measured in 20 chromium exposed workers(exposure group) and in 11 chromium workers(control group) who were not exposed. The concentration of 8-OH-dG in their urine was determined using high performance liquid chromatography with electrochemical detection. RESULTS: The blood chromium concentration was significantly higher in the exposure group ( 0.46+/-0.18 microgram/100 ml) than in control group(0.27+/-0.15 microgram/100 ml), but the urinary chromium concentration was not significantly higher in the exposure group. The urinary 8-OH-dG was higher in the exposure group(1.71+/-1.82 micromol/mol creatinine) than that in the control group(0.45+/-0.46 micromol/mol creatinine) and was significantly correlated with the blood chromium concentration(r=0.49). Results of multiple regression analysis revealed that the level of urinary 8-OH-dG depended upon the level of the blood chromium conc entration ( r2= 0.21). CONCLUSIONS: Urinary 8-OH-dG was significantly related to chromium exposure and this finding suggests the possibility that urinary 8-OH-dG could be used as a biological index of chromium induced DNA damage.
Biological Markers ; Chromatography, Liquid ; Chromium* ; DNA ; DNA Damage

OBJECT: The aim of this study is to determine whether exposure to chlorpromazine causes mutagenicity and genetic disorders. METHOD: Ames (Salmonella typhimurium) test and Rec assay (Bacillus subtilis) were used as indicators for DNA damage. Furthermore, the levels of umu operon expression by measuring the beta-galactosidase activity were monitered with the SOS umu test using S. typhimurium 1535 containing plasmid pSK1002. And the host-mediated assay was used to investigate the muta-genicity of chlorpromazine after the activation with in vivo metabolic systems. RESULTS: From the results, chlorpromazine did not affect DNA of S. typhimurium and B. subtilis strains and showed no mutagenicity at the all concentrations tested. These phenomena was also similar to that after metabolic activation of chlorpromazine in in vivo system. CONCLUSION: These results suggested that chlorpromazine did not show the mutagenicity and genotoxicity by four different methods used in this study.
beta-Galactosidase ; Biotransformation ; Chlorpromazine* ; DNA ; DNA Damage ; Operon ; Plasmids

BACKGROUND: Recently the sensitive measurement of radiation damage to DNA using flowcytometric analysis of nucleoid preparations was reported which allows an analysis of damage within the DNA of single cells. We applied flowcytometric analysis of the nucleoids for the detection of DNA damage by UVB. OBJECTIVE: The purpose of this study was to establish the method of detecting UVB-induced damage of DNA by flowcytometry and to elucidate the usefulness of this method to detect cell damage. METHODS: Human melanoma cells were cultured and were irradiated with various of UVB. Immediately after UVB irradiation nucleoid suspensions were prepared and flowcytometric analysis was done. RESULTS: The changes in fluorescence, forward scatter, and side scatter reflected damage of DNA induced by UVB quite well especially at lower UVB doses. CONCLUSION: Flowcytometric analysis of nucleoid will be a useful methosd to detect DNA damage by UVB.
DNA ; DNA Damage ; Fluorescence ; Humans ; Melanoma ; Methods ; Suspensions ; Ultraviolet Rays*

Comet Assay ; DNA Damage ; DNA Repair ; In Situ Hybridization, Fluorescence ; methods

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).
Recombinational DNA Repair ; DNA-Binding Proteins/metabolism* ; DNA Repair ; DNA Damage ; DNA