Urinary N3 adenine DNA adducts in humans occupationally exposed to styrene

Mikeš, Petr; Kořínek, Marek; Linhart, Igor; Krouželka, Jan; Dabrowská, Ludmila; Stránský, Vladimír; Mráz, Jaroslav

doi:10.1016/j.toxlet.2010.05.015

Cited by 4 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA adducts can be released from the DNA backbone and excreted in urine as free nucleobases as a result of their spontaneous depurination , or their active repair via base excision repair pathways . Previous studies have detected urinary nucleobase adducts induced by estrogens, lipid peroxidation products, N -ethyl- N -nitrosourea, and reactive metabolites of environmental chemicals such as polyaromatic hydrocarbons and styrene . Although nucleobase adducts found in urine may have sources other than DNA (for example, from RNA or cellular nucleoside pools), urinary adducts can serve as a biomarker of carcinogen exposure and metabolic activation to DNA-reactive species.…”

Section: Discussionmentioning

confidence: 99%

Isotope Dilution nanoLC/ESI⁺-HRMS³ Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

Sangaraju¹,

Boldry²,

Patel

et al. 2017

Chem. Res. Toxicol.

View full text Add to dashboard Cite

1,3-Butadiene (BD) is an important industrial and environmental chemical classified as a known human carcinogen. Occupational exposure to BD in the polymer and monomer industries is associated with an increased incidence of lymphoma. BD is present in automobile exhaust, cigarette smoke, and forest fires, raising concern about potential exposure of general population to this carcinogen. Following inhalation exposure, BD is bioactivated to 3,4-epoxy-1-butene (EB). If not detoxified, EB is capable of modifying guanine and adenine bases of DNA to form nucleobase adducts, which interfere with accurate DNA replication and cause cancer-initiating mutations. We have developed a nanoLC/ESI+-HRMS3 methodology for N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts in human urine (limit of detection: 0.25 fmol/mL urine, limit of quantitation: 1.0 fmol/mL urine). The new method was successfully used to quantify EB-GII in urine of F344 rats treated with 0 – 200 ppm BD, occupationally exposed workers, and smokers belonging to two different ethnic groups. EB-GII amounts increased in a dose-dependent manner in urine of laboratory rats exposed to 0, 62.5, or 200 ppm BD. Urinary EB-GII levels were significantly increased in workers occupationally exposed to 0.1–2.2 ppm BD (1.25 ± 0.51pg/mg creatinine) as compared to administrative controls exposed to < 0.01 ppm BD (0.22 ± 0.08 and pg/mg creatinine) (p = 0.0024), validating the use of EB-GII as a biomarker of human exposure to BD. EB-GII was also detected in smokers’ urine, with European American smokers excreting significantly higher amounts of EB-GII than African American smokers (0.48 ± 0.09 vs 0.12 ± 0.02 pg/mg creatinine, p = 3.1 × 10−7). Interestingly, small amounts of EB-GII were observed in animals and humans with no known exposure to BD, providing preliminary evidence for its endogenous formation. Comparison of EB-GII adduct levels in urine to urinary mercapturic acids of BD (MHBMA, DHBMA) and genetic polymorphisms were also attempted in the genotyped smoker ethnic groups cohort.

show abstract

Section: Discussionmentioning

confidence: 99%

Isotope Dilution nanoLC/ESI⁺-HRMS³ Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

Sangaraju¹,

Boldry²,

Patel

et al. 2017

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…These data suggest that previously characterized depurinating AF adducts ,, are sufficiently stable in cells to contribute directly to cellular responses and/or that biologically important and chemically stable AF–DNA adducts are as yet uncharacterized. Further research needed to reconcile these toxicological possibilities, which are important not only for these molecules but of fundamental relevance to addressing biological responses of DNA-reactive cytotoxins on a chemical level. − …”

Section: Repair Of Acylfulvene-induced Dna Damagementioning

confidence: 99%

Chemistry and Biology of Acylfulvenes: Sesquiterpene-Derived Antitumor Agents

Tanasova

Sturla

2012

Chem. Rev.

View full text Add to dashboard Cite

“…Other adducts are excreted in a nucleotide or nucleoside form following repair by nucleotide excision repair mechanism [ 50 , 51 , 52 ] and/or nucleolytic degradation of DNA [ 53 , 54 ]. Earlier studies have described urinary DNA adducts induced by endogenous biomolecules such as estrogens [ 55 ], lipid peroxidation products [ 56 ] as well as by reactive exogenous metabolites such as styrene [ 57 ] and polyaromatic hydrocarbons [ 58 ]. Previous studies employed BD-derived urinary adduct, EB-GII, as a useful biomarker of exposure to BD and metabolic activation [ 34 , 35 , 36 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine

Erber

Goodman

Krueger

et al. 2021

Toxics

View full text Add to dashboard Cite

1,3-Butadiene (BD) is a common environmental and industrial chemical widely used in plastic and rubber manufacturing and also present in cigarette smoke and automobile exhaust. BD is classified as a known human carcinogen based on evidence of carcinogenicity in laboratory animals treated with BD by inhalation and epidemiological studies revealing an increased risk of leukemia and lymphohematopoietic cancers in workers occupationally exposed to BD. Upon exposure via inhalation, BD is bioactivated to several toxic epoxides including 3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB); these are conjugated with glutathione and excreted as 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA). Exposure to DEB generates monoalkylated DNA adducts, DNA-DNA crosslinks, and DNA-protein crosslinks, which can cause base substitutions, genomic rearrangements, and large genomic deletions. In this study, we developed a quantitative nanoLC/NSI+-HRMS methodology for 1,4-bis-(gua-7-yl)-2,3-butanediol (bis-N7G-BD) adducts in urine (LOD: 0.1 fmol/mL urine, LOQ: 1.0 fmol/mL urine). This novel method was used to quantify bis-N7G-BD in urine of mice treated with 590 ± 150 ppm BD for 2 weeks (6 h/day, 5 days/week). Bis-N7G-BD was detected in urine of male and female BD-exposed mice (574.6 ± 206.0 and 571.1 ± 163.4 pg/mg of creatinine, respectively). In addition, major urinary metabolites of BD, bis-BDMA, MHBMA and DHBMA, were measured in the same samples. Urinary bis-N7G-BD adduct levels correlated with DEB-derived metabolite bis-BDMA (r = 0.80, Pearson correlation), but not with the EB-derived DNA adducts (EB-GII) or EB-derived metabolites MHBMA and DHBMA (r = 0.24, r = 0.14, r = 0.18, respectively, Pearson correlations). Urinary bis-N7G-BD could be employed as a novel non-invasive biomarker of exposure to BD and bioactivation to its most mutagenic metabolite, DEB. This method will be useful for future studies of 1,3-butadiene exposure and metabolism.

show abstract

Urinary N3 adenine DNA adducts in humans occupationally exposed to styrene

Cited by 4 publications

References 36 publications

Isotope Dilution nanoLC/ESI⁺-HRMS³ Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

Isotope Dilution nanoLC/ESI⁺-HRMS³ Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

Chemistry and Biology of Acylfulvenes: Sesquiterpene-Derived Antitumor Agents

Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine

Contact Info

Product

Resources

About

Urinary N3 adenine DNA adducts in humans occupationally exposed to styrene

Cited by 4 publications

References 36 publications

Isotope Dilution nanoLC/ESI+-HRMS3 Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

Isotope Dilution nanoLC/ESI+-HRMS3 Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

Chemistry and Biology of Acylfulvenes: Sesquiterpene-Derived Antitumor Agents

Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine

Contact Info

Product

Resources

About

Isotope Dilution nanoLC/ESI⁺-HRMS³ Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

Isotope Dilution nanoLC/ESI⁺-HRMS³ Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene