Analysis of crotonaldehyde- and acetaldehyde-derived 1,n(2)-propanodeoxyguanosine adducts in DNA from human tissues using liquid chromatography electrospray ionization tandem mass spectrometry - PubMed (original) (raw)

Analysis of crotonaldehyde- and acetaldehyde-derived 1,n(2)-propanodeoxyguanosine adducts in DNA from human tissues using liquid chromatography electrospray ionization tandem mass spectrometry

Siyi Zhang et al. Chem Res Toxicol. 2006 Oct.

Abstract

Crotonaldehyde, a mutagen and carcinogen, reacts with deoxyguanosine (dGuo) in DNA to generate a pair of diastereomeric 1,N(2)()-propanodeoxyguanosine adducts (Cro-dGuo, 2), which occur in (6S,8S) and (6R,8R) configurations. They can also be formed through the consecutive reaction of two acetaldehyde molecules with dGuo. Cro-dGuo adducts inhibit DNA synthesis and induce miscoding in human cells. Considering their potential role in carcinogenesis, we have developed a sensitive and specific liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method to explore the presence of Cro-dGuo adducts in DNA from various human tissues, such as liver, lung, and blood. DNA was isolated from human tissues and enzymatically hydrolyzed to deoxyribonucleosides. [(15)N(5)]Cro-dGuo was synthesized and used as an internal standard. The Cro-dGuo adducts were enriched from the hydrolysate by solid-phase extraction and analyzed by LC-ESI-MS/MS using selected reaction monitoring (SRM). This method allows the quantitation of the Cro-dGuo adducts at a concentration of 4 fmol/micromol dGuo, corresponding to about 1 adduct per 10(9) normal nucleosides starting with 1 mg of DNA, with high accuracy and precision. DNA from human liver, lung, and blood was analyzed. The Cro-dGuo adducts were detected more frequently in human lung DNA than in liver DNA but were not detected in DNA from blood. The results of this study provide quantified data on Cro-dGuo adducts in human tissues. The higher frequency of Cro-dGuo in lung DNA than in the other tissues investigated is potentially important and deserves further study.

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Figures

Figure 1

Chromatograms obtained upon LC-ESI-MS/MS analysis of 0.5 fmol standard Cro-dGuo (2) (top) and 10 fmol [15N5]Cro-dGuo ([15N5]2) (bottom). Peak areas were 4.9*104 for (6S, 8S)-2, 5.5*104 for (6R, 8R)-2, 1.1*106 for (6S, 8S)-[15N5]2, and 1.2*106 for (6R, 8R)-[15N5]2.

Figure 2

Calibration curves for Cro-dGuo (2, 0.5–50 fmol) and [15N5]Cro-dGuo ([15N5]2, 10 fmol): ■, (6S, 8S)-2, R2 = 1.0000;, ρ, (6R, 8R)-2, R2 = 1.0000.

Figure 3

Chromatograms obtained upon LC-ESI-MS/MS analysis of calf thymus DNA. Calf thymus DNA was enzymatically hydrolyzed, purified by SPE, and analyzed (panel A); or the eluants from SPE were treated with NaOH and NaBH4 and analyzed (panel B). Transitions of m/z 340 → m/z 224 and m/z 345 → m/z 229 correspond to the ring-opened products of the analyte and internal standard, N2_-(4-hydroxybut-2-yl)dGuo and [15N5]N2_-(4-hydroxybut-2-yl)dGuo, respectively. The early eluting peak was produced from (6_R, 8R)-2 and the late eluting peak from (6_S, 8S)-2.

Figure 4

Relationship of added to detected Cro-dGuo (2). Various amounts of standard adduct 2 were added to calf thymus DNA (0.91 mg) containing [15N5]2 and analyzed by the method described in the text. Adduct 2 in calf thymus DNA [9.80 fmol/mg DNA for (6S, 8S)-2 and 8.49 fmol/mg DNA for (6R, 8R)-2] was subtracted from each amount detected. Each point represents a triplicate measurement. A, (6S, 8S)-2, R2 = 0.9986; B, (6R, 8R)-2, R2 = 1.0000.

Figure 5

Chromatograms obtained upon LC-ESI-MS/MS-SRM analysis of DNA from human liver and lung. A and C, DNA from human liver; B, DNA from the same human liver as in A, to which 2 fmol of each diastereomer of Cro-dGuo was added; D, DNA from human lung.

Scheme 1

Formation of _1,N2_-propanodeoxyguanosine adducts in the reactions of crotonaldehyde or acetaldehyde with dGuo.

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References

1. International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 63. IARC; Lyon, France: 1995. Dry cleaning, some chlorinated solvents and other industrial chemicals; pp. 373–391. - PMC - PubMed
1. Chung FL, Chen HJ, Nath RG. Lipid peroxidation as a potential endogenous source for the formation of exocyclic DNA adducts. Carcinogenesis. 1996;17:2105–2111. - PubMed
1. Wang MY, Chung FL, Hecht SS. Identification of crotonaldehyde as a hepatic microsomal metabolite formed by α-hydroxylation of the carcinogen N-nitrosopyrrolidine. Chem Res Toxicol. 1988;1:28–31. - PubMed
1. Neudecker T, Eder E, Deininger C, Henschler D. Crotonaldehyde is mutagenic in Salmonella typhimurium TA100. Environ Mol Mutagen. 1989;14:146–148. - PubMed
1. Chung FL, Tanaka T, Hecht SS. Induction of liver tumors in F344 rats by crotonaldehyde. Cancer Res. 1986;46:1285–1289. - PubMed

Analysis of crotonaldehyde- and acetaldehyde-derived 1,n(2)-propanodeoxyguanosine adducts in DNA from human tissues using liquid chromatography electrospray ionization tandem mass spectrometry - PubMed (original) (raw)