1-Methoxy-3-indolylmethyl DNA adducts in six tissues, and blood protein adducts, in mice under pak choi diet: time course and persistence

Wiesner-Reinhold, Melanie; Barknowitz, Gitte; Florian, Simone; Mewis, Inga; Schumacher, Fabian; Schreiner, Monika; Glatt, Hansruedi

doi:10.1007/s00204-019-02452-3

Cited by 6 publications

(8 citation statements)

References 48 publications

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“…Mice, rather than rats, were used due to their smaller body weight to reduce the quantities of test materials required. In an additional study, pak choi powder (prepared from lyophilised sprouts) and total GLs extract were mixed to the feed in a mouse study (up to 8-day treatment and up to 16-day follow-up under standard diet) (Wiesner-Reinhold et al 2019 ). The main messages: (1) 1-MIM DNA adducts were detected in all models; (2) the tissue distribution of the adduct varied substantially depending, on the test material, the time of analysis and the presence or absence of intestinal bacteria; (3) adducts in gut were eliminated rapidly via cell renewal; (4) in other tissues (with low cell turnover), adducts were rather persistent and they accumulated after repeated dosing.…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of DNA damage response, e.g. p53 accumulation and/or increased expression of p53-dependent genes was a common effect of treatment with GBS or 1-MIM alcohol (Ehlers et al 2015 ; Schumacher et al 2014 ; Wiesner-Reinhold et al 2019 ). However, we found no indications for xenometabolic adaptation (decreased activation/increased detoxification of the test material) after repeated dosing.…”

Section: Discussionmentioning

confidence: 99%

“…However, we found no indications for xenometabolic adaptation (decreased activation/increased detoxification of the test material) after repeated dosing. This conclusion was primarily inferred from the time courses of adducts in haemoglobin and serum albumin (Barknowitz et al 2014 ; Wiesner-Reinhold et al 2019 ), as protein adducts, in contrast to many DNA adducts, are not actively repaired in general. However, all these studies were conducted with individual test compounds (1-MIM GL or 1-MIM alcohol) or a matrix containing particularly high levels of 1-MIM-GL (pak choi sprouts elicited with methyl jasmonate, mimicking an attack by chewing and phloem-sucking insects).…”

Section: Discussionmentioning

confidence: 99%

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Feeding Brassica vegetables to rats leads to the formation of characteristic DNA adducts (from 1-methoxy-3-indolylmethyl glucosinolate) in many tissues

et al. 2022

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Juices of Brassica vegetables are mutagenic and form characteristic DNA adducts in bacteria and mammalian cells. In this study, we examined whether such adducts are also formed in vivo in animal models. Rats fed raw broccoli ad libitum in addition to normal laboratory chow for 5 weeks showed one major adduct spot and sometimes an additional minor adduct spot in liver, kidney, lung, blood and the gastrointestinal tract, as determined by 32P-postlabelling/thin-layer chromatography. Adducts with the same chromatographic properties were formed when herring sperm DNA (or dG-3’-phosphate) was incubated with 1-methoxy-3-indolylmethyl glucosinolate (phytochemical present in Brassica plants), in the presence of myrosinase (plant enzyme that hydrolyses glucosinolates to bioactive breakdown products). UPLC–MS/MS analysis corroborated this finding: 1-Methoxy-3-indolylmethyl-substituted purine nucleosides were detected in the hepatic DNA of broccoli-fed animals, but not in control animals. Feeding raw cauliflower led to the formation of the same adducts. When steamed rather than raw broccoli was used, the adduct levels were essentially unchanged in liver and jejunum, but elevated in large intestine. Due to inactivation of myrosinase by the steaming, higher levels of the glucosinolates may have reached the large bowl to be activated by glucosidases from intestinal bacteria. In conclusion, the consumption of common Brassica vegetables can lead to the formation of substantial levels of DNA adducts in animal models. The adducts can be attributed to a specific phytochemical, neoglucobrassicin (1-methoxy-3-indolylmethyl glucosinolate).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Feeding Brassica vegetables to rats leads to the formation of characteristic DNA adducts (from 1-methoxy-3-indolylmethyl glucosinolate) in many tissues

et al. 2022

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“…Adducts with histidines are found for: a) natural products - pyrrolizidine alkaloids (Ma et al 2019 ), 1-methoxy-3-indolylmethyl glucosinolate (Barknowitz et al 2014 ; Wiesner-Reinhold et al 2019 ).…”

Section: Protein Adductsmentioning

confidence: 99%

Quo vadis blood protein adductomics?

Sabbioni

Day²

2021

Arch Toxicol

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Chemicals are measured regularly in air, food, the environment, and the workplace. Biomonitoring of chemicals in biological fluids is a tool to determine the individual exposure. Blood protein adducts of xenobiotics are a marker of both exposure and the biologically effective dose. Urinary metabolites and blood metabolites are short term exposure markers. Stable hemoglobin adducts are exposure markers of up to 120 days. Blood protein adducts are formed with many xenobiotics at different sites of the blood proteins. Newer methods apply the techniques developed in the field of proteomics. Larger adducted peptides with 20 amino acids are used for quantitation. Unfortunately, at present the methods do not reach the limits of detection obtained with the methods looking at single amino acid adducts or at chemically cleaved adducts. Therefore, to progress in the field new approaches are needed.

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“…There are evidences presented for exciting protective effects of many other GSLs, but they are not commercially available [56,57]. The same could be said for the indoles, with the literature focusing to an absurd degree on compounds that happen to be commercially available, although they are not necessarily the most widespread in vegetables [58], or when comparing a non-substituted and a substituted indole [59].…”

Section: Future Perspectives and Challengesmentioning

confidence: 99%

The Role of Brassica Bioactives on Human Health: Are We Studying It the Right Way?

Quirante-Moya¹,

García-Ibáñez

Quirante-Moya

et al. 2020

Molecules

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Brassica vegetables and their components, the glucosinolates, have been suggested as good candidates as dietary coadjutants to improve health in non-communicable diseases (NCDs). Different preclinical and clinical studies have been performed in the last decade; however, some concerns have been posed on the lack of established and standardized protocols. The different concentration of bioactive compounds used, time of intervention or sample size, and the lack of blinding are some factors that may influence the studies’ outcomes. This review aims to analyze the critical points of the studies performed with Brassica-related biomolecules and propose some bases for future trials in order to avoid biases.

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1-Methoxy-3-indolylmethyl DNA adducts in six tissues, and blood protein adducts, in mice under pak choi diet: time course and persistence

Cited by 6 publications

References 48 publications

Feeding Brassica vegetables to rats leads to the formation of characteristic DNA adducts (from 1-methoxy-3-indolylmethyl glucosinolate) in many tissues

Feeding Brassica vegetables to rats leads to the formation of characteristic DNA adducts (from 1-methoxy-3-indolylmethyl glucosinolate) in many tissues

Quo vadis blood protein adductomics?

The Role of Brassica Bioactives on Human Health: Are We Studying It the Right Way?

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