Formation and persistence of O6-(2-hydroxyethyl)-2′-deoxyguanosine in DNA of various rat tissues following a single dose of N-nitroso-N-(2-hydroxyethyl)urea. An immuno-slot-blot study

Lüdeke, Barbara; Kleihues, Paul

doi:10.1093/carcin/9.1.147

Cited by 28 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recovery of radioactivity from urine after 12 h (20% of the total administered radioactivity) was slightly higher in the present experiment than reported previously (13), which could reflect the excretion of polar radiolysis products of [methyll4 C]-NMBzA. When [methyl- 14 C]NMBzA was given 3 h after DAS, formation of I4 CC»2 was markedly retarded, with a total of 49% of the administered radioactivity released within 10 h (f W[ ™» = 3 h). In contrast, production of I4 CC>2 from [methyl-C]-NMBzA administered 18 h after DAS was complete within 6 h (%", = 1.8 h), whereas the fraction exhaled as I4 CC>2 was decreased to 42 %.…”

contrasting

confidence: 70%

“…Conversely, preadministration with DAS has been shown to result in inactivation and subsequent removal from the microsomal membrane of hepatic cytochrome P4502E1 within 18 h (8,9). We observed a decrease in both the extent and rate of formation of 14 CO 2 from [methyl- 14 C]NMBzA given 18 h after a single dose of DAS, suggesting that a significant reduction of nitrosamine bioactivation may be achieved after repeated administrations of DAS through modulation of cytochrome P450 enzyme levels in target cells. However, although NMBzA is preferentially bioactivated in the oesophageal mucosa, measurements of overall metabolism in the intact animal primarily reflect hepatic turnover because of the size of the liver (17,18) and cannot necessarily be extrapolated to other organs.…”

mentioning

confidence: 78%

“…DNA was isolated by automated phenolic extraction using a Model 340A Nucleic Acid Extractor (Applied Biosystems, Inc., Foster City, CA) as described previously (12), except that tissue homogenates were filtered through nylon gauze (30 /tm mesh; Willi Fischer Labortechnik, Frankfurt/Main, Germany). Methylated deoxyguanosines were quantitated by immuno-slot-blot assays using rabbit antiserum NPZ-193 to O^-methyldeoxyguanosine (C^-MEdG) (14) and an antiserum to imidazole ring-opened 7-methyldeoxyguanosine (7-MEdG) (15) essentially as described elsewhere (16) were almost identical to those observed previously (13,18). Recovery of radioactivity from urine after 12 h (20% of the total administered radioactivity) was slightly higher in the present experiment than reported previously (13), which could reflect the excretion of polar radiolysis products of [methyll4 C]-NMBzA.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Modulation of N-nitrosomethylbenzylamine bioactivation by diallyl sulfide in vivo

et al. 1992

Self Cite

View full text Add to dashboard Cite

Diallyl sulfide (DAS*), a major flavour and fragrance component of garlic oil (1), has been shown to be an effective inhibitor of tumorigenesis by diverse metabolically activated chemical carcinogens <2-5). In the most striking example of chemoprevention, Wargovich and co-workers reported (4) that pretreatment with DAS completely prevented the formation in rat oesophagus of both malignant and premalignant lesions by /V-nitrosomethylbenzylamine (NMBzA), an exceptionally potent and selective oesophageal carcinogen in this species (6). After preadministration of DAS, a significant reduction has been observed in nuclear aberrations induced by NMBzA and dimethylhydrazine (4,7) but not in the nucleotoxicity of the direct-acting methylating•Abbreviations: DAS, diallyl sulfide; NMBzA, N-nitrosomethylbenzylamine; O^-MEdG, C^-methyldeoxyguanosine, 7-MEdG, 7-methyldeoxyguanosine.© Oxford University Press carcinogens /V-nitrosomethylurea and /V-methyl-/V'-nitro-/Vnitrosoguanidine (7). Studies in vitro have shown that DAS also is an inhibitor of oxidative metabolism by cytochrome P450 enzymes of a number of carcinogenic nitrosamines, including NMBzA, /V-nitrosodimethylamine, /V-nitrosodiethylamine and 4-(A'-memyl-A^-nirjosarnino)-l-(3-pyridyl)-l-butanone (4,(8)(9)(10). These findings suggested that DAS may block nitrosamineinduced tumorigenesis by inhibiting nitrosamine bioactivation in situ. In the present investigation, we have examined this possibility by assessing the effects of DAS on the overall metabolism of NMBzA and on DNA methylation by NMBzA in vivo.In the protocol developed by Wargovich and co-workers (4), rats received five weekly treatments consisting of an i.g. dose of 200 mg/kg of DAS followed 3 h later by a s.c. injection of 3.5 mg/kg of NMBzA. However, in vitro demethylation of NMBzA was significantly lower by hepatic microsomes prepared 18 h after a similar dose of DAS than by microsomes collected 3 h post-treatment (8). In order to determine whether there is a similar difference in vivo between immediate and delayed effects of DAS on overall NMBzA metabolism, we monitored the formation of 14 CO 2 and radioactive urinary metabolites from [methyll4

show abstract

contrasting

confidence: 70%

mentioning

confidence: 78%

mentioning

confidence: 99%

See 1 more Smart Citation

Modulation of N-nitrosomethylbenzylamine bioactivation by diallyl sulfide in vivo

et al. 1992

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the present study, we used a rabbit antiserum to C^-methyldeoxyguanosine (12). When this technique was applied to oesophagi of rats chronically exposed to NMBzA or NM2MBA in the drinking water, only very few immunoreactive cells were detected in the basal layer of the adjacent oesophageal mucosa, in regions with dysplasia and in papiilomas (not shown).…”

Section: Resultsmentioning

confidence: 96%

“…Monoclonal anti-BUdR antibody was from Becton-Dickinson, Basel, Switzerland. Characteristics of the rabbit antiserum raised against keyhole limpet haemocyanin conjugates of C^-methylguanosine (NPZ 193-1) have been described earlier (12). The antiserum was used without prior absorption.…”

Section: Chemicals and Antibodiesmentioning

confidence: 99%

Bioactivation of N-nitrosomethylbenzylamine and N-nitrosomethyl-amylamine in oesophageal papillomas

Dirsch

Koenigsmann²,

Lüdeke³

et al. 1990

Carcinogenesis

View full text Add to dashboard Cite

AGT Activity Towards Intrastrand Crosslinked DNA is Modulated by the Alkylene Linker

O’Flaherty

Wilds

2017

ChemBioChem

View full text Add to dashboard Cite

DNA oligomers containing dimethylene and trimethylene intrastrand crosslinks (IaCLs) between the O4 and O6 atoms of neighboring thymidine (T) and 2'-deoxyguanosine (dG) residues were prepared by solid-phase synthesis. UV thermal denaturation (T ) experiments revealed that these IaCLs had a destabilizing effect on the DNA duplex relative to the control. Circular dichroism spectroscopy suggested these IaCLs induced minimal structural distortions. Susceptibility to dealkylation by reaction with various O -alkylguanine DNA alkyltransferases (AGTs) from human and Escherichia coli was evaluated. It was revealed that only human AGT displayed activity towards the IaCL DNA, with reduced efficiency as the IaCL shortened (from four to two methylene linkages). Changing the site of attachment of the ethylene linkage at the 5'-end of the IaCL to the N3 atom of T had minimal influence on duplex stability and structure, and was refractory to AGT activity.

show abstract

Formation and persistence of O⁶-(2-hydroxyethyl)-2′-deoxyguanosine in DNA of various rat tissues following a single dose of N-nitroso-N-(2-hydroxyethyl)urea. An immuno-slot-blot study

Cited by 28 publications

References 28 publications

Modulation of N-nitrosomethylbenzylamine bioactivation by diallyl sulfide in vivo

Modulation of N-nitrosomethylbenzylamine bioactivation by diallyl sulfide in vivo

Bioactivation of N-nitrosomethylbenzylamine and N-nitrosomethyl-amylamine in oesophageal papillomas

AGT Activity Towards Intrastrand Crosslinked DNA is Modulated by the Alkylene Linker

Contact Info

Product

Resources

About