Identification of Octenal-Related dA and dC Adducts Formed by Reactions with a Hemin-ω-6-fat Peroxidation Model System

Kawai, Kazuaki; Kawasaki, Yukako; Kubota, Yumiko; Kimura, Tomoyuki; Sawa, Ryûichi; Matsuda, Tomonari; Kasai, Hiroshi

doi:10.1021/tx400245a

Cited by 4 publications

(2 citation statements)

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“…The challenges that we currently face are that many of the identified spots (a distinct mass per charge and retention time) do not have any annotations . We have been able to measure as many as 174 species of known DNA adducts, and the numbers of adducts will continue to increase with the addition of newly characterized adducts and the introduction of instruments with higher specifications. Another challenge is that identification does not necessarily mean quantification.…”

Section: Approaches From the Practice Of Pathology To Investigating Tmentioning

confidence: 99%

Susceptibility to human cancer: From the perspective of a pathologist

Sugimura

2016

Pathology International

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The etiologies of human cancer can only be discerned when the genetic clustering of cancer occurs within a family or when cancer occurs endemically in a particular environment. The possible approaches to solving the nature/nurture problem, especially for human carcinogenesis, posit a fascinating challenge for pathologists. This perspective review presents some examples of how clues to human cancer etiologies and/or susceptibilities reside in the realm of pathology practice. These examples using various omics techniques including adductomics, which I would like to highlight in this article, show that the currently available concepts and methods in human pathology can open a path toward the brave new world of a post-genomic era of medicine for young pathologists, whether their original intention was toward the pursuit of diagnostic or investigative knowledge.

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Section: Approaches From the Practice Of Pathology To Investigating Tmentioning

confidence: 99%

Susceptibility to human cancer: From the perspective of a pathologist

Sugimura

2016

Pathology International

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“…Next, we examined adduct formation between nucleosides and an ω-6 fat peroxidation model system [ 52 ]. Based on the literature, ω-6 fat, rather than ω-3-fat, and red meat seem to be more important risk factors in relation to colon cancer [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

What causes human cancer? Approaches from the chemistry of DNA damage

Kasai

2016

Genes and Environ

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To prevent human cancers, environmental mutagens must be identified. A common mechanism of carcinogenesis is DNA damage, and thus it is quite possible that environmental mutagens can be trapped as adducts by DNA components. It is also important to identify new types of DNA damaging reactions and clarify their mechanisms. In this paper, I will provide typical examples of our efforts to identify DNA damage by environmental agents, from chemistry-based studies. 1) Oxidative DNA damage: 8-Hydroxydeoxyguanosine (8-OHdG, 8-oxodG) was discovered during a structural study of DNA modifications caused in vitro by heating glucose, which was used as a model of cooked foods. We found that various oxygen radical-forming agents induced the formation of 8-OHdG in DNA, in vitro and in vivo. Analyses of the urinary 8-OHdG levels are useful to assess the extent of oxidative DNA damage in a human population. 2) Lipid peroxide-derived DNA adducts: We searched for mutagens that react with deoxynucleosides, in model systems of lipid peroxidation. The reaction mixtures were analyzed by high performance liquid chromatography (HPLC), and we discovered various lipid peroxide-derived mutagens, including new mutagens. Some of these adducts were detected in human DNA. These mutagens may be involved in lipid peroxide-related cancers. 3) Methylation of cytosine by free radicals: Methylation of the cytosine C-5 position is an important mechanism of carcinogenesis, in addition to gene mutations. However, the actual mechanisms of de novo methylation in relation to environmental agents are not clear. We found that cytosine C-5 methylation occurred by a free radical mechanism. The possible role of this radical-induced DNA methylation in carcinogenesis will be discussed, in relation to the presently accepted concept of cancer epigenetics. In these studies, chemical analyses of the adducts formed in model reactions led to the discoveries of new mutagens and important types of DNA modifications, which seem to be involved in human carcinogenesis.

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