Sucrose and IQ induced mutations in rat colon by independent mechanism

Hansen, Max; Hald, Mikkel Thomas; Autrup, Herman; Vogel, Ulla; Bornholdt, Jette; Möller, Peter; Mølck, Anne‐Marie; Lindecrona, R. H.; Poulsen, Henrik E.; Wallin, Håkan; Loft, Steffen; Dragsted, Lars Ove

doi:10.1016/j.mrfmmm.2004.05.002

Cited by 8 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, these do not seem to be underlying mechanisms of NAFLD and NASH in this particular animal model. The null results on hepatic DNA damage is in keeping with earlier results in rats showing no altered levels of DNA strand breaks after feeding with saturated fats [ 55 ] and sucrose [ 56 – 59 ]. Alternatively, livers may have to become cirrhotic before notable telomere shortening can be detected, which may also explain the absence of telomere shortenings.…”

Section: Discussionsupporting

confidence: 90%

High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundNon-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD.MethodsSeventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high-fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 % cholesterol) for 16 and 25 weeks.ResultsAll three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001), LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p < 0.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p < 0.01) compared to control and vHS.ConclusionCollectively, our results suggest that intake of fat and cholesterol, but not sucrose, are the main factors driving the development and progression of dyslipidemia and NAFLD/NASH.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0110-1) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 90%

High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…High intake of sucrose is associated with increased risk of colon cancer [ 99 ]. Co-mutagenic effects of sucrose were examined in colon of 2-amino-3-methylimidazo[4,5- f ]quinoline (IQ)-treated Big Blue rats [ 100 ]. Sucrose and IQ increased the mutation frequencies and the combined treatment with sucrose and IQ was additive, indicating that sucrose and IQ induce mutations independently.…”

Section: Transgenic Rats For Mutagenesismentioning

confidence: 99%

“… Liver cII + Ibid Colon cII + Ibid *No effect of Se. Sucrose Big Blue rat (F344) 30 % Diet Male 9–12 35/35 Liver cII - [101] Colon cII +− Ibid 34.50 % Diet Male 8–12 21/21 Liver cII - [ 136 ] Colon cII + ibid 13.80 % Diet Male 8–12 21/21 Liver cII - Ibid Colon cII + Ibid 6.90 % Diet Male 8–12 21/21 Liver cII - Ibid Colon cII - Ibid 13.40 % Diet Male 9–12 21/21 Liver cII - [ 100 ] Colon cII + Ibid 3.45 % Diet Male 9–12 21/21 Liver cII - Ibid Colon cII ...…”

Section: Introductionmentioning

confidence: 99%

Transgenic rat models for mutagenesis and carcinogenesis

2017

View full text Add to dashboard Cite

Rats are a standard experimental animal for cancer bioassay and toxicological research for chemicals. Although the genetic analyses were behind mice, rats have been more frequently used for toxicological research than mice. This is partly because they live longer than mice and induce a wider variety of tumors, which are morphologically similar to those in humans. The body mass is larger than mice, which enables to take samples from organs for studies on pharmacokinetics or toxicokinetics. In addition, there are a number of chemicals that exhibit marked species differences in the carcinogenicity. These compounds are carcinogenic in rats but not in mice. Such examples are aflatoxin B1 and tamoxifen, both are carcinogenic to humans. Therefore, negative mutagenic/carcinogenic responses in mice do not guarantee that the chemical is not mutagenic/carcinogenic to rats or perhaps to humans. To facilitate research on in vivo mutagenesis and carcinogenesis, several transgenic rat models have been established. In general, the transgenic rats for mutagenesis are treated with chemicals longer than transgenic mice for more exact examination of the relationship between mutagenesis and carcinogenesis. Transgenic rat models for carcinogenesis are engineered mostly to understand mechanisms underlying chemical carcinogenesis. Here, we review papers dealing with the transgenic rat models for mutagenesis and carcinogenesis, and discuss the future perspective.

show abstract

“…There were no interactions between IQ and sucrose interms of induction of mutations. [ 129 ] 2-amino-3-methylimidazo[4,5- f ]quinoline (IQ) S.D. rats female diet for 13 weeks gpt liver 300 ppm + G:C to T:A transversions and single guanine deletions were induced by IQ.…”

Section: Introductionmentioning

confidence: 99%

Mutagenicity of carcinogenic heterocyclic amines in Salmonella typhimurium YG strains and transgenic rodents including gpt delta

Nohmi

Watanabe

2021

Genes and Environ

View full text Add to dashboard Cite

Chemical carcinogens to humans have been usually identified by epidemiological studies on the relationships between occupational or environmental exposure to the agents and specific cancer induction. In contrast, carcinogenic heterocyclic amines were identified under the principle that mutagens in bacterial in the Ames test are possible human carcinogens. In the 1970s to 1990s, more than 10 heterocyclic amines were isolated from pyrolysates of amino acids, proteins, meat or fish as mutagens in the Ames test, and they were demonstrated as carcinogens in rodents. In the 1980s and 1990s, we have developed derivatives of the Ames tester strains that overexpressed acetyltransferase of Salmonella typhimurium. These strains such as Salmonella typhimurium YG1024 exhibited a high sensitivity to the mutagenicity of the carcinogenic heterocyclic amines. Because of the high sensitivity, YG1024 and other YG strains were used for various purposes, e.g., identification of novel heterocyclic amines, mechanisms of metabolic activation, comparison of mutagenic potencies of various heterocyclic amines, and the co-mutagenic effects. In the 1990s and 2000s, we developed transgenic mice and rats for the detection of mutagenicity of chemicals in vivo. The transgenics were generated by the introduction of reporter genes for mutations into fertilized eggs of mice and rats. We named the transgenics as gpt delta because the gpt gene of Escherichia coli was used for detection of point mutations such as base substitutions and frameshifts and the red/gam genes of λ phage were employed to detect deletion mutations. The transgenic rodents gpt delta and other transgenics with lacI or lacZ as reporter genes have been utilized for characterization of mutagenicity of heterocyclic amines in vivo. In this review, we summarized the in vitro mutagenicity of heterocyclic amines in Salmonella typhimurium YG strains and the in vivo mutagenicity in transgenic rodents. We discussed the relationships between in vitro and in vivo mutagenicity of the heterocyclic amines and their relations to the carcinogenicity.

show abstract

Sucrose and IQ induced mutations in rat colon by independent mechanism

Cited by 8 publications

References 23 publications

High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

Transgenic rat models for mutagenesis and carcinogenesis

Mutagenicity of carcinogenic heterocyclic amines in Salmonella typhimurium YG strains and transgenic rodents including gpt delta

Contact Info

Product

Resources

About