DNA adducts in marine fish as biological marker of genotoxicity in environmental monitoring: The way forward
30
Citation
120
Reference
10
Related Paper
Citation Trend
Keywords:
DNA adduct
Xenobiotic
We have employed the P1-enhanced 32P-postlabeling procedure to detect the formation DNA of adducts in the white blood cells (WBC) of B6C3F1 mice treated by i.p. injection with benzene. Treatment twice a day with 440 mg/kg benzene for 1–7 days resulted in the formation of one major (adduct 1) and one minor (adduct 2) DNA adduct in the WBCs of mice. The same DNA adduct pattern was also found in the bone marrow (BM) of benzene treated mice. The relative adduct levels were dependent upon both benzene dose from 100–440 mg/kg and treatment time from 1 to 7 days. The relative adduct levels ranged between 0.11 and 1.33 adducts in 107 nucleotides for WBCs and 0.16–1.21 adducts in 107 nucleotides for BM. Following treatment with benzene, the levels of DNA adducts formed in WBCs were significantly correlated with the levels of DNA adducts formed in BM (r2 = 0.97, P <0.001). Our results suggest that measurement of DNA adducts in WBCs may be an indicator of DNA adduct formation in BM following BZ exposure.
White (mutation)
Cite
Citations (18)
Treatment of EMT6 mouse mammary tumor cells with mitomycin C (MC) results in the formation of six major MC−DNA adducts. We identified the last unknown of these ("adduct X") as a guanine N2 adduct of 2,7-diaminomitosene (2,7-DAM), in which the mitosene is linked at its C-10 position to guanine N2. The assigned structure is based on UV and mass spectra of adduct X isolated directly from the cells, as well as on its difference UV, second-derivative UV, and circular dichroism spectra, synthesis from [8-3H]deoxyguanosine, and observation of its heat stability. These tests were carried out using 17 μg of synthetic material altogether. The mechanism of formation of adduct X involves reductive metabolism of MC to 2,7-DAM, which undergoes a second round of reductive activation to alkylate DNA, yielding adduct X and another 2,7-DAM−guanine adduct (adduct Y), which is linked at guanine N7 to the mitosene. Adduct Y has been described previously. Adduct X is formed preferentially at GpC, while adduct Y favors the GpG sequence. In contrast to MC−DNA adducts, the 2,7-DAM−DNA adducts are not cytotoxic.
Mitomycin C
Mammary carcinoma
Mammary tumor
Cite
Citations (29)
DNA adduct
Phenazine
Cite
Citations (6)
DNA adduct
Cite
Citations (13)
Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome) analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA) against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC), revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.
DNA adduct
Cite
Citations (46)
DNA adduct
Cite
Citations (34)
Xenobiotic
Hemolymph
In vitro toxicology
Comet Assay
Marine invertebrates
Environmental toxicology
Cite
Citations (22)
Spectrophotometry
Cite
Citations (21)
DNA adduct
Cite
Citations (13)
The endogenous mutagenic/carcinogenic 9- (4'-aminophenyl) -9H- pyrido [3,4-b] indole (aminophenylnorharman, APNH) is formed from norharman and aniline in the presence of cytochrome P-450s. The major APNH-DNA adduct has been reported to be 2'-deoxyguanosin-8-yl-aminophenylnorhaman (dG-C8-APNH). In addition, demonstrated formation of APNH-RNA adduct and conducted a structural analysis using various spectrometric approaches. The compound produced from guanosine (Guo) and N-acetoxy-APNH, an ultimate mutagenic form of APNH, was concluded to be guanosin-8-yl-APNH (Guo-C8-APNH) on the basis of various spectroscopic analysis. The same adduct was found in the livers of rats administered APNH. The total adduct levels of APNH-RNA were six times higher than total APNH-DNA adducts in the same rat liver samples.
DNA adduct
Cite
Citations (2)