+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Ethanol and 4-methylpyrazole increase DNA adduct formation of furfuryl alcohol in FVB/N wild-type mice and in mice expressing human sulfotransferases 1A1/1A2



Ethanol and 4-methylpyrazole increase DNA adduct formation of furfuryl alcohol in FVB/N wild-type mice and in mice expressing human sulfotransferases 1A1/1A2



Carcinogenesis 37(3): 314-319



Furfuryl alcohol (FFA) is a carcinogenic food contaminant, which is formed by acid- and heat-catalyzed degradation of fructose and glucose. The activation by sulfotransferases (SULTs) yields a DNA reactive and mutagenic sulfate ester. The most prominent DNA adduct, N(2)-((furan-2-yl)methyl)-2'-deoxyguanosine (N(2)-MF-dG), was detected in FFA-treated mice and also in human tissue samples. The dominant pathway of FFA detoxification is the oxidation via alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs). The activity of these enzymes may be greatly altered in the presence of inhibitors or competitive substrates. Here, we investigated the impact of ethanol and the ADH inhibitor 4-methylpyrazole (4MP) on the DNA adduct formation by FFA in wild-type and in humanized mice that were transgenic for human SULT1A1/1A2 and deficient in the mouse (m) Sult1a1 and Sult1d1 genes (h1A1/1A2/1a1(-)/1d1(-)). The administration of FFA alone led to hepatic adduct levels of 4.5 N(2)-MF-dG/10(8) nucleosides and 33.6 N(2)-MF-dG/10(8) nucleosides in male and female wild-type mice, respectively, and of 19.6 N(2)-MF-dG/10(8) nucleosides and 95.4 N(2)-MF-dG/10(8) nucleosides in male and female h1A1/1A2/1a1(-)/1d1(-) mice. The coadministration of 1.6g ethanol/kg body weight increased N(2)-MF-dG levels by 2.3-fold in male and by 1.7-fold in female wild-type mice and by 2.5-fold in male and by 1.5-fold in female h1A1/1A2/1a1(-)/1d1(-) mice. The coadministration of 100mg 4MP/kg body weight had a similar effect on the adduct levels. These findings indicate that modulators of the oxidative metabolism, e.g. the drug 4MP or consumption of alcoholic beverages, may increase the genotoxic effects of FFA also in humans.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057800671

Download citation: RISBibTeXText

PMID: 26775039

DOI: 10.1093/carcin/bgw006


Related references

Formation of DNA adducts in wild-type and transgenic mice expressing human sulfotransferases 1A1 and 1A2 after oral exposure to furfuryl alcohol. Mutagenesis 30(5): 643-649, 2016

Study of 5-hydroxymethylfurfural and its metabolite 5-sulfooxymethylfurfural on induction of colonic aberrant crypt foci in wild-type mice and transgenic mice expressing human sulfotransferases 1A1 and 1A2. Molecular Nutrition and Food Research 56(4): 593-600, 2012

The effect of knockout of sulfotransferases 1a1 and 1d1 and of transgenic human sulfotransferases 1A1/1A2 on the formation of DNA adducts from furfuryl alcohol in mouse models. Carcinogenesis 35(10): 2339-2345, 2015

Metabolic activation of furfuryl alcohol: formation of 2-methylfuranyl DNA adducts in Salmonella typhimurium strains expressing human sulfotransferase 1A1 and in FVB/N mice. Carcinogenesis 32(10): 1533-1539, 2011

Hemoglobin adducts of furfuryl alcohol in genetically modified mouse models: Role of endogenous sulfotransferases 1a1 and 1d1 and transgenic human sulfotransferases 1A1/1A2. Toxicology Letters 295: 173-178, 2018

Toxicity studies with 5-hydroxymethylfurfural and its metabolite 5-sulphooxymethylfurfural in wild-type mice and transgenic mice expressing human sulphotransferases 1A1 and 1A2. Archives of Toxicology 86(5): 701-711, 2012

Strong impact of sulfotransferases on DNA adduct formation by 4-aminobiphenyl in bladder and liver in mice. Cancer Medicine 7(11): 5604-5610, 2018

Self administration of ethanol and 4 methylpyrazole augments chronic self exposure to alcohol in c57bl 6j mice. Alcoholism Clinical & Experimental Research 12(2): 304, 1988

Defective B cell ontogeny and humoral immune response in mice prematurely expressing human complement receptor 2 (CR2, CD21) is similar to that seen in aging wild type mice. Molecular Immunology 46(10): 2002-2013, 2009

The effect of pentachlorophenol on DNA adduct formation in p53 wild-type and knockout mice exposed to benzo[a]pyrene. Cancer Letters 178(1): 11-17, 2002

Benzo[a]pyrene (BP) DNA adduct formation in DNA repair-deficient p53 haploinsufficient [Xpa(-/-)p53(+/-)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days. Carcinogenesis 33(11): 2236-2241, 2013

The influence of the SULT1A status - wild-type, knockout or humanized - on the DNA adduct formation by methyleugenol in extrahepatic tissues of mice. Toxicology Research 5(3): 808-815, 2016

Distinct mechanisms of axonal globule formation in mice expressing human wild type α-synuclein or dementia with Lewy bodies-linked P123H β-synuclein. Molecular Brain 5: 34, 2013

Distinct mechanisms of axonal globule formation in mice expressing human wild type alpha-synuclein or dementia with Lewy bodies-linked P123H Ss-synuclein. 2012

Mice expressing mutations in Fas and Fas ligand demonstrate less corneal pathology and mortality than do wild-type mice following infection with HSV-1. IOVS 42(4): S109, March 15, 2001