Possible Genetic Risks from Heat-Damaged DNA in Food

Jun, Yong Woong; Kant, Melis; Coskun, Erdem; Kato, Takamitsu A.; Jaruga, Pawel; Palafox, Elizabeth; Dizdaroglu, Miral; Kool, Eric T.

doi:10.1021/acscentsci.2c01247

Cited by 9 publications

(3 citation statements)

References 46 publications

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“…DietNAs are food components that are gaining researchers' attention not only because of their nutritional value, which has been already utilized by manufacturers of dietary supplements [23,24], but also because of the potential risks associated with excessive consumption of modified dietNAs contained in processed food [25]. The knowledge of dietNA content and distribution in various food products is necessary information from the perspective of research on their nutritional properties.…”

Section: Discussionmentioning

confidence: 99%

Microscopic Imaging to Visualize the Distribution of Dietary Nucleic Acids in Food Products of Various Origins

Kościelak,

Koziara,

Maria

et al. 2023

Foods

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Dietary nucleic acids (dietNAs) are being increasingly recognized as important food components with nutritional value. However, the precise dietary recommendations for dietNAs are limited, because established methods for determining the quantity and nutritional role of dietNAs are still lacking. One of the tools to narrow this gap could be microscopic imaging, as a convenient approach to visualize the abundance and distribution of dietNAs in food products. With the aid of appropriate bioinformatic elaboration, such images may in future enable the direct semiquantitative estimation of these macromolecules in food products. In the presented study, two methods of preparing microscopic sections and staining them with DNA-specific fluorochromes were used for microscopic imaging of dietNAs in food products of plant and animal origin. Procedures for preparing formalin-fixed paraffin-embedded sections and cryosections were compared in terms of their usefulness for routine food analysis. Both methods turned out equally suitable for visualizing dietNA distribution in animal and plant products. However, the use of cryosections allowed a significantly shorter analysis time and reduced the consumption of organic solvents. Both of these advantages make the cryosection method preferable while establishing a dedicated methodology for routine assessment of dietNAs in the food industry.

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Section: Discussionmentioning

confidence: 99%

Microscopic Imaging to Visualize the Distribution of Dietary Nucleic Acids in Food Products of Various Origins

Kościelak,

Koziara,

Maria

et al. 2023

Foods

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“…Digested food is another source of damaged dNTPs that find their way into cellular DNA (30). Pol b incorporates 8-OxodGuoMP opposite dA ~40-times more efficiently than opposite dC, promoting genomic mutations (31).…”

Section: Introductionmentioning

confidence: 99%

Biochemical and Structural Characterization of Fapy•dG Replication by Human DNA Polymerase β

Gao,

Oden,

Ryan

et al. 2024

Preprint

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N6-(2-deoxy-α,β-D-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy·dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). Fapy·dG preferentially gives rise to G to T transversions and G to A transitions. However, the molecular basis by which Fapy·dG is processed by DNA polymerases during this mutagenic process remains poorly understood. To address this we investigated how DNA polymerase β (Pol β), a model mammalian polymerase, bypasses a templating Fapy·dG, inserts Fapy·dGTP, and extends from Fapy·dG at the primer terminus. When Fapy·dG is present in the template, Pol β incorporates TMP less efficiently than either dCMP or dAMP. Kinetic analysis revealed that Fapy·dGTP is a poor substrate but is incorporated ~3-times more efficiently opposite dA than dC. Extension from Fapy·dG at the 3'-terminus of a nascent primer is inefficient due to the primer terminus being poorly positioned for catalysis. Together these data indicate that mutagenic bypass of Fapy·dG is likely to be the source of the mutagenic effects of the lesion and not Fapy·dGTP. These experiments increase our understanding of the promutagenic effects of Fapy·dG.

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“…Promutagenic base pairs are also produced as a result of oxidation of the dNTP pool and subsequent damaged nucleotide monophosphate incorporation into DNA by polymerases. Digested food is another source of damaged dNTPs that find their way into cellular DNA ( 30 ). Pol β incorporates 8-OxodGuoMP opposite dA ∼40-times more efficiently than opposite dC, promoting genomic mutations ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

Biochemical and structural characterization of Fapy•dG replication by Human DNA polymerase β

Gao,

Oden,

Ryan

et al. 2024

Nucleic Acids Research

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N6-(2-deoxy-α,β-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy•dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OxodGuo). Fapy•dG preferentially gives rise to G → T transversions and G → A transitions. However, the molecular basis by which Fapy•dG is processed by DNA polymerases during this mutagenic process remains poorly understood. To address this we investigated how DNA polymerase β (Pol β), a model mammalian polymerase, bypasses a templating Fapy•dG, inserts Fapy•dGTP, and extends from Fapy•dG at the primer terminus. When Fapy•dG is present in the template, Pol β incorporates TMP less efficiently than either dCMP or dAMP. Kinetic analysis revealed that Fapy•dGTP is a poor substrate but is incorporated ∼3-times more efficiently opposite dA than dC. Extension from Fapy•dG at the 3′-terminus of a nascent primer is inefficient due to the primer terminus being poorly positioned for catalysis. Together these data indicate that mutagenic bypass of Fapy•dG is likely to be the source of the mutagenic effects of the lesion and not Fapy•dGTP. These experiments increase our understanding of the promutagenic effects of Fapy•dG.

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Possible Genetic Risks from Heat-Damaged DNA in Food

Cited by 9 publications

References 46 publications

Microscopic Imaging to Visualize the Distribution of Dietary Nucleic Acids in Food Products of Various Origins

Microscopic Imaging to Visualize the Distribution of Dietary Nucleic Acids in Food Products of Various Origins

Biochemical and Structural Characterization of Fapy•dG Replication by Human DNA Polymerase β

Biochemical and structural characterization of Fapy•dG replication by Human DNA polymerase β

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