Oxidative DNA and RNA damage in rat liver due to acetoxime: similarity to effects of 2-nitropropane

Hussain, Nalband; Conaway, C. Clifford; Nie, Guoxing; Asaad, Wagdy; Fiala, Emerich S.

doi:10.1093/carcin/11.6.1013

Cited by 29 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The development of the nucleic acid modifications DX1 and 8-aminoguanosine and the increased formation of 8-oxoguanine in DNA and RNA were detected also after administration of the ketoximes acetone oxime (Guo et al 1990;), 3-pentanone oxime, 4-heptanone oxime (Hussain et al 1991), cyclopentanone oxime (Conaway et al 1991) and cyclohexanone oxime (Hussain et al 1991) and of the secondary nitroalkanes 2-nitropropane, 2-nitrobutane, 3-nitropentane, 2-nitroheptane, 2-nitrooctane and nitrocyclopentane (Conaway et al 1991). The ketoximes were less effective than their oxidation products, the corresponding secondary nitroalkanes (Guo et al 1990;Hussain et al 1990). The DNA-modifying effects of both substance groups were stronger in male animals than in females (Guo et al 1990).…”

Section: In Vivomentioning

confidence: 98%

“…It has been suggested that also the DNA-damaging effects of the ketoximes result from in vivo oxidation to the corresponding secondary nitroalkanes (Fiala et al 1995;Hussain et al 1990); Mirvish et al 1982, which are metabolized in the liver in asulfotransferase-dependent reaction to form areactive, DNA-binding species.…”

Section: M Echanism Of Actionmentioning

confidence: 99%

“…The findings described in Section 5.6.2 (Genotoxicity in vivo)r egarding the formation of modified nucleosides by butanone oxime and structurally related ketoximes, indicate that there is another metabolic pathway for the ketoximes investigated which is connected with their genotoxic effects. It has been suggested that the DNA-damaging effects of the ketoximes result from their in vivo oxidation to form the corresponding secondary nitroalkanes (Fiala et al 1995;Hussain et al 1990;Mirvish et al 1982). Oxidation of acetone oxime-albeit very slight-to form propane-2-nitronate, the anion of 2nitropropane, has been demonstrated in liver microsomes of the rat, mouse and humans (Kohl et al 1992).…”

Section: T Oxicokinetics and Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

Butanone oxime [MAK Value Documentation, 2013]

2013

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

Supplement 1997 MAK value/classification see Section III, Category 2ofthe List of MAK and BAT Values Date of evaluation 1997 CAS number 96-29-7Since publication of the documentation from 1979 documentation "Butanonoxim" 1979 (German), further studies have yielded results which make it necessary to reevaluate the substance. 1T oxic Effects and Mode of ActionButanone oxime is taken up orally, dermally and by inhalation. The substance has strong local irritative effects on the mucous membranes. After long-term exposure of rats and mice, damage to the olfactory epithelium was observed even at the lowest concentration tested of 15 ml/m 3 . Methaemoglobin was produced after short-term exposure to concentrations of 400 ml/m 3 and above; concentrations of around 700 ml/m 3 and above led to sedative and narcotic effects with hypoactivity after aphase of agitation. After repeated exposure for up to ay ear, methaemoglobin was formed even at concentrations of 100 ml/m 3 ,w hile adaptation was observed after long-term exposure. Enlargement and pigmentation of the spleen, and extramedullary haematopoiesis in the liver are connected with the erythrocyte-damaging effects of butanone oxime.After long-term inhalation, the most important effects are the hepatotoxic effects in addition to the damage to the olfactory epithelium. In male rats and mice, toxic effects on the liver were observed after concentrations of 15 ml/m 3 as well as the local effects. After concentrations of 75 ml/m 3 and above, the incidence of liver adenomas in male rats was increased, and butanone oxime concentrations of 375 ml/m 3 led to asignificant increase in the incidence of liver carcinomas in the male animals. The occurrence of DNA and RNA modifications in the liver of rats exposed to butanone oxime indicates al iver-specific activation of butanone oxime to produce metabolites with genotoxic potential.In in vitro genotoxicity studies, except for one positive mouse lymphoma test without metabolic activation, mostly negative results were obtained (Salmonella mutagenicity test, and tests for sister chromatid exchange (SCE), unscheduled

show abstract

Section: In Vivomentioning

confidence: 98%

Section: M Echanism Of Actionmentioning

confidence: 99%

Section: T Oxicokinetics and Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Butanone oxime [MAK Value Documentation, 2013]

2013

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

show abstract

“…Other reports have demonstrated that F-344 rats are more prone than S-D rats to develop inflammatory granulomas when exposed to various chemicals and pharmaceutical agents [Ward et al, 1993;Schwab, 1977a, 1977b]. F-344 rats are more susceptible than S-D rats to oxidative stress in the liver, as measured by necrosis and DNA adduct formation, when exposed to diquat [Smith et al, 1985] and 2-nitropropane [Hussain et al, 1990].…”

Section: Introductionmentioning

confidence: 98%

Differences in the response to oxidative stress and mutant frequency in CD (Sprague-Dawley) and Fisher 344 rats due to an induced inflammatory response

Sams

Blaydes

Warbritton

et al. 2000

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

In this study, the rodent air pouch model was used to examine the production and processing of oxidative DNA damage in two strains of rats commonly used in toxicity testing. An inflammatory response was induced by injecting zymosan A (50 mg) into an air pouch on male CD (Sprague‐Dawley [S‐D]) and Fisher 344 (F‐344) rats, and the animals were then sacrificed at 1, 3, 7, 14, and 28 days (n = 6 per time point per strain). Tissues from the lining of the air pouch were collected for 8‐hydroxy‐2′‐deoxyguanosine (8‐OH‐dG) analysis and for paraffin embedding. Significant (P < 0.01) increases in 8‐OH‐dG were observed after 1 day in the DNA from cells lining the air pouch of zymosan A‐treated versus control S‐D (101.5 ± 27.1 vs. 23.1 ± 2.7 8‐OH‐dG/dG × 105) and F‐344 (51.4 ± 5.3 vs. 14.4 ± 0.6 8‐OH‐dG/dG × 105) rats. By 28 days, 8‐OH‐dG levels had returned to background in S‐D rats, but remained elevated in F‐344 rats. The frequency of apoptosis was evaluated using the in situ end‐labeling (TUNEL) assay, which revealed that zymosan A‐treated S‐D rats had a significantly (P < 0.05) higher frequency of apoptosis compared to zymosan A‐treated F‐344 rats. To examine the potential consequences of these differences in endogenously produced DNA damage and apoptosis, we measured mutations at the hprt locus in fibroblasts of the pouch lining and observed a significant (P < 0.05) increase in the mutant frequency at day 28 in F‐344 rats (54.2 ± 13.6 mutants per 106 cells) compared to controls (4.5 ± 2.0 mutants per 106 cells). The mutant frequency was not increased in S‐D rats. These data demonstrate that strain differences in the production and processing of oxidative DNA damage due to an inflammatory response may impact the long‐term pathologic consequences of chronic inflammation. Environ. Mol. Mutagen. 35:336–342, 2000 Published 2000 Wiley‐Liss, Inc.

show abstract

“…It has been reported that high doses of methyl ethyl ketoxime may induce hematopoietic and central nervous system dysfunctions and result in developmental abnormalities (Schulze & Derelanko, 1993; Burka et al ., 1998; Derelanko et al ., 2003). Some ketoximes have also been suggested to act as hepatocarcinogens in rats because their oral and intraperitoneal administrations have been reported to increase 8‐hydroxyguanine levels in the liver DNAs and RNAs of male Sprague Dawley and F344 rats (Hussain et al ., 1990). …”

Section: Introductionmentioning

confidence: 99%

Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

et al. 2015

View full text Add to dashboard Cite

SummaryPhenyl‐2‐pyridyl ketoxime (PPKO) was found to be one of the small molecules enriched in the extracellular matrix of near‐senescent human diploid fibroblasts (HDFs). Treatment of young HDFs with PPKO reduced the viability of young HDFs in a dose‐ and time‐dependent manner and resulted in senescence‐associated β‐galactosidase (SA‐β‐gal) staining and G2/M cell cycle arrest. In addition, the levels of some senescence‐associated proteins, such as phosphorylated ERK1/2, caveolin‐1, p53, p16ink4a, and p21waf1, were elevated in PPKO‐treated cells. To monitor the effect of PPKO on cell stress responses, reactive oxygen species (ROS) production was examined by flow cytometry. After PPKO treatment, ROS levels transiently increased at 30 min but then returned to baseline at 60 min. The levels of some antioxidant enzymes, such as catalase, peroxiredoxin II and glutathione peroxidase I, were transiently induced by PPKO treatment. SOD II levels increased gradually, whereas the SOD I and III levels were biphasic during the experimental periods after PPKO treatment. Cellular senescence induced by PPKO was suppressed by chemical antioxidants, such as N‐acetylcysteine, 2,2,6,6‐tetramethylpiperidinyloxy, and L‐buthionine‐(S,R)‐sulfoximine. Furthermore, PPKO increased nitric oxide (NO) production via inducible NO synthase (iNOS) in HDFs. In the presence of NOS inhibitors, such as L‐NG‐nitroarginine methyl ester and L‐NG‐monomethylarginine, PPKO‐induced transient NO production and SA‐β‐gal staining were abrogated. Taken together, these results suggest that PPKO induces cellular senescence in association with transient ROS and NO production and the subsequent induction of senescence‐associated proteins.

show abstract

Oxidative DNA and RNA damage in rat liver due to acetoxime: similarity to effects of 2-nitropropane

Cited by 29 publications

References 0 publications

Butanone oxime [MAK Value Documentation, 2013]

Butanone oxime [MAK Value Documentation, 2013]

Differences in the response to oxidative stress and mutant frequency in CD (Sprague-Dawley) and Fisher 344 rats due to an induced inflammatory response

Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

Contact Info

Product

Resources

About