Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice

Okamura, Tomio; Ishii, Yuji; Suzuki, Yuta; Inoue, Tomoki; Tasaki, Masayuki; Kodama, Yukio; Nohmi, Takehiko; Mitsumori, Kunitoshi; Umemura, Takashi; Nishikawa, Akiyoshi

doi:10.2131/jts.35.731

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…Our previous data demonstrated that the spontaneous gpt MFs in the colon of male C57BL/6 gpt delta mice at 11 weeks of age was 0.82±0.43 (Means±SD, n=5) (Okamura et al, 2010). The values at 19 and 32 weeks of age in the present study were 0.38±0.12 and 0.95±0.64, respectively.…”

Section: Discussionsupporting

confidence: 62%

No Effect of High Fat Diet-Induced Obesity on Spontaneous Reporter Gene Mutations in gpt Delta Mice

Takasu

Ishii²,

Matsushita³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or Spi -mutant frequencies between STD-and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations.

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Section: Discussionsupporting

confidence: 62%

No Effect of High Fat Diet-Induced Obesity on Spontaneous Reporter Gene Mutations in gpt Delta Mice

Takasu

Ishii²,

Matsushita³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Instead, Polk −/− mice exhibited much higher sensitivity to the mutagenicity of DSS than Polk +/+ mice. These results were surprising because DSS was known to be non-mutagenic both in vitro and in vivo [ 26 , 27 ]. In fact, DSS did not induce mutations in Polk +/+ mice in a previous study [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

DNA polymerase κ suppresses inflammation and inflammation-induced mutagenesis and carcinogenic potential in the colon of mice

et al. 2023

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Background Chronic inflammation induces DNA damage and promotes cell proliferation, thereby increasing the risk of cancer. DNA polymerase κ (Pol κ), involved in translesion DNA synthesis, counteracts mutagenesis induced by inflammation in the colon of mice. In the present study, we examined whether Pol κ suppressed inflammation-induced colon tumorigenesis by treating inactivated Polk knock-in (Polk−/−) mice with dextran sulfate sodium (DSS), an inducer of colon inflammation. Results Male and female Polk−/− and Polk+/+ mice were administered 2% DSS in drinking water for six consecutive days, succeeded via a recovery period of 16 days, followed by 2% DSS for another two days. DSS treatment strongly induced colitis, and the severity of colitis was higher in Polk−/− mice than in Polk+/+ mice. The mice were sacrificed after 19 weeks from the initiation of the first DSS treatment and subjected to pathological examination and mutation analysis. DSS treatment induced colonic dysplasia, and the multiplicity of dysplasia was higher in Polk−/− mice than in Polk+/+mice. Some of the dysplasias in Polk−/− mice exhibited β-catenin-stained nucleus and/or cytoplasm. Mutation frequencies in the gpt reporter gene were increased by DSS treatment in Polk−/− mice, and were higher than those in Polk+/+ mice. Conclusions Pol κ suppresses inflammation and inflammation-induced dysplasia as well as inflammation-induced mutagenesis. The possible mechanisms by which Pol κ suppresses colitis- and colitis-induced dysplasia are discussed.

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“…Such assays are promising tools for investigating the relationship between chemical genotoxicity and carcinogenicity. As additional analyses, various factors related to chemical carcinogenesis, such as DNA modifications, oxidative stress, cell proliferation and metabolic enzyme activities can also be measured in transgenic rodents [4][5][6][7][8][9][10][11] . This review focuses on reported renal carcinogens found in natural products such as d-limonene and aristolochic acid (AA), food additives such as potassium bromate (KBrO 3 ) and madder color (MC), and mycotoxins such as ochratoxin A (OTA) and citrinin (CTN).…”

Section: Introductionmentioning

confidence: 99%

Possible Carcinogenic Mechanisms Underlying Renal Carcinogens in Food

Umemura

2014

Food Safety

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Some chemicals contained in foods originating from a variety of sources including natural plants, food additives, residual pesticides, mycotoxins and by-products created during food processing and/or cooking have previously been demonstrated to be carcinogenic at various sites in rodents. This review focuses on reported renal carcinogens in natural products such as d-limonene and aristolochic acid (AA), food additives such as potassium bromate (KBrO 3 ) and madder color (MC), as well as mycotoxins such as ochratoxin A (OTA) and citrinin (CTN) and discusses data from reporter gene mutation assays. In addition to in vivo genotoxicity, recent information on several factors related to chemical carcinogenesis, such as DNA modifications and cell proliferation, gave insight into possible modes of action that underlie renal carcinogenesis. Given that neither d-limonene nor CTN induced increases in mutant frequencies (MFs) in some reporter genes, cell proliferation at target sites arising from compensatory and/or direct mitogenic action may play a key role in the carcinogenic mechanism of these compounds. Clear positive results from reporter gene mutation assays for AA, MC and OTA strongly suggest that genotoxic mechanisms are involved in carcinogenesis induced by these agents. While KBrO 3 elevated MFs in the red/gam gene (Spi − ), it did so to a lower extent than did potent genotoxic carcinogens. Accordingly, the participation of genotoxic mechanisms in KBrO 3 -induced renal carcinogenesis may be limited.

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Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice

Cited by 7 publications

References 23 publications

No Effect of High Fat Diet-Induced Obesity on Spontaneous Reporter Gene Mutations in gpt Delta Mice

No Effect of High Fat Diet-Induced Obesity on Spontaneous Reporter Gene Mutations in gpt Delta Mice

DNA polymerase κ suppresses inflammation and inflammation-induced mutagenesis and carcinogenic potential in the colon of mice

Possible Carcinogenic Mechanisms Underlying Renal Carcinogens in Food

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