Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice
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{"title"=>"Chlorinated water modulates the development of colorectal tumors with chromosomal instability and gut microbiota in Apc-deficient mice", "type"=>"journal", "authors"=>[{"first_name"=>"Tatsunari", "last_name"=>"Sasada", "scopus_author_id"=>"36673825600"}, {"first_name"=>"Takao", "last_name"=>"Hinoi", "scopus_author_id"=>"6603342104"}, {"first_name"=>"Yasufumi", "last_name"=>"Saito", "scopus_author_id"=>"55575148300"}, {"first_name"=>"Tomohiro", "last_name"=>"Adachi", "scopus_author_id"=>"37066941000"}, {"first_name"=>"Yuji", "last_name"=>"Takakura", "scopus_author_id"=>"26537970300"}, {"first_name"=>"Yasuo", "last_name"=>"Kawaguchi", "scopus_author_id"=>"35601506100"}, {"first_name"=>"Yusuke", "last_name"=>"Sotomaru", "scopus_author_id"=>"6602798522"}, {"first_name"=>"Kazuhiro", "last_name"=>"Sentani", "scopus_author_id"=>"6507430004"}, {"first_name"=>"Naohide", "last_name"=>"Oue", "scopus_author_id"=>"6604018116"}, {"first_name"=>"Wataru", "last_name"=>"Yasui", "scopus_author_id"=>"18345300300"}, {"first_name"=>"Hideki", "last_name"=>"Ohdan", "scopus_author_id"=>"7006495986"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"84940850253", "doi"=>"10.1371/journal.pone.0132435", "scopus"=>"2-s2.0-84940850253", "isbn"=>"1932-6203", "pmid"=>"26186212", "pui"=>"605870684"}, "id"=>"b8e9bb15-c6ad-341c-99dc-025261e73231", "abstract"=>"The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc) knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma--caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc(+/flox), abbreviated to CPC;Apc) or microsatellite (CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox)) instability, respectively--were administered chlorinated (10.0 mg/L chlorine) or tap (0.7 mg/L chlorine) water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox) mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to differences in gastrointestinal commensal populations.", "link"=>"http://www.mendeley.com/research/chlorinated-water-modulates-development-colorectal-tumors-chromosomal-instability-gut-microbiota-apc", "reader_count"=>23, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Other"=>3, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Other"=>3, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>5, "Design"=>1, "Psychology"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Germany"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2180430"], "description"=>"<p><b>A,</b> X-gal activity in cecal crypt in a 20-week-old <i>CDX2P9</i>.<i>5-G19Cre;R26R</i> mouse. ce, cecum; co, colon; an, anus. Bar, 10 mm. <b>B,</b> Stereomicrograph (45×) of the cecal epithelium (small box) with X-gal and eosin staining of a 20-week-old <i>CDX2P9</i>.<i>5-G19Cre;R26R</i> mouse. Bar, 1 mm. <b>C,</b> Quantitative analysis of X-gal staining in 20-week-old <i>CDX2P9</i>.<i>5-G19Cre;R26R</i> mice. Cells were counted in six fields; data represent mean ± SD. <b>D,</b> Dissected ileum and colorectal tract of <i>CDX2P9</i>.<i>5-G22 Cre;Apc</i><sup><i>flox/flox</i></sup> mice with cecum-proximal tumors. Left, tissue sample from a 15-week-old mouse treated with chlorinated water (10.0 mg/mL). Right, tissue sample from a 15-week-old mouse treated with tap water (0.7 mg/mL). Bar, 10 mm.</p>", "links"=>[], "tags"=>["cpc", "CDX 2P", "knockout mouse models", "colon polyp formation", "colorectal cancer", "Chlorinated Water Modulates", "chlorine", "nls", "chlorinated drinking water", "anaerobes Clostridium perfringens", "tumorigenesi", "tumor", "CDX 2P instability", "adenomatous polyposis coli", "CDX 2P mice", "drinking water influence"], "article_id"=>1486832, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Tatsunari Sasada", "Takao Hinoi", "Yasufumi Saito", "Tomohiro Adachi", "Yuji Takakura", "Yasuo Kawaguchi", "Yusuke Sotomaru", "Kazuhiro Sentani", "Naohide Oue", "Wataru Yasui", "Hideki Ohdan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132435.g004", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cre_activation_in_CDX2P9_5_G19Cre_R26R_mice_/1486832", "title"=>"Cre activation in <i>CDX2P9</i>.<i>5-G19Cre;R26R</i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-17 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2180431"], "description"=>"<p>*Mean bacterial counts (log<sub>10</sub> cells/g) per 1 g of feces from four mice in each group.</p><p>Fecal bacteria in mice treated with chlorinated or tap water<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132435#t001fn001\" target=\"_blank\">*</a></sup>.</p>", "links"=>[], "tags"=>["cpc", "CDX 2P", "knockout mouse models", "colon polyp formation", "colorectal cancer", "Chlorinated Water Modulates", "chlorine", "nls", "chlorinated drinking water", "anaerobes Clostridium perfringens", "tumorigenesi", "tumor", "CDX 2P instability", "adenomatous polyposis coli", "CDX 2P mice", "drinking water influence"], "article_id"=>1486833, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Tatsunari Sasada", "Takao Hinoi", "Yasufumi Saito", "Tomohiro Adachi", "Yuji Takakura", "Yasuo Kawaguchi", "Yusuke Sotomaru", "Kazuhiro Sentani", "Naohide Oue", "Wataru Yasui", "Hideki Ohdan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132435.t001", "stats"=>{"downloads"=>5, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fecal_bacteria_in_mice_treated_with_chlorinated_or_tap_water_/1486833", "title"=>"Fecal bacteria in mice treated with chlorinated or tap water<sup>*</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-17 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2180427"], "description"=>"<p><b>A,</b> Tumorigenesis in 40-week-old <i>CPC;Apc</i> mice. Left, mouse administered chlorinated water (10.0 mg/L chlorine). Right, mouse administered tap water (0.7 mg/L chlorine). Tumors were mainly detected in the colon and at the end of the ileum in the chlorinated and tap water groups, respectively. st, stomach; je, jejunum; ce, cecum; co, colon; an, anus. Bar, 10 mm. <b>B,</b> Tumor histology in <i>CPC;Apc</i> mice. H&E staining of a colonic tumor from a chlorinated water-treated mouse (left) and a small intestinal tumor from a tap water-treated mouse (right). Bar, 500 μm. <b>C,</b> Body weight gain in the chlorinated water group (black box) was the same as in wild-type C57B/6 mice, while the tap water group (white box) had significantly lower weight gain. *P < 0.05 (ANOVA).</p>", "links"=>[], "tags"=>["cpc", "CDX 2P", "knockout mouse models", "colon polyp formation", "colorectal cancer", "Chlorinated Water Modulates", "chlorine", "nls", "chlorinated drinking water", "anaerobes Clostridium perfringens", "tumorigenesi", "tumor", "CDX 2P instability", "adenomatous polyposis coli", "CDX 2P mice", "drinking water influence"], "article_id"=>1486829, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Tatsunari Sasada", "Takao Hinoi", "Yasufumi Saito", "Tomohiro Adachi", "Yuji Takakura", "Yasuo Kawaguchi", "Yusuke Sotomaru", "Kazuhiro Sentani", "Naohide Oue", "Wataru Yasui", "Hideki Ohdan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132435.g001", "stats"=>{"downloads"=>10, "page_views"=>127, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumorigenesis_and_body_weight_in_CPC_Apc_mice_/1486829", "title"=>"Tumorigenesis and body weight in <i>CPC;Apc</i> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-17 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2180428"], "description"=>"<p>A greater number of polyps was detected in the colon than in the ileum of the chlorinated water group (black columns), whereas more polyps occurred in the small intestine in the tap water group (white columns). Polyp volume was correlated with polyp number, and colon polyp volume differed significantly between the two groups. ch; chlorinated water group, ta; tap water group. *P < 0.05 (Student’s t test).</p>", "links"=>[], "tags"=>["cpc", "CDX 2P", "knockout mouse models", "colon polyp formation", "colorectal cancer", "Chlorinated Water Modulates", "chlorine", "nls", "chlorinated drinking water", "anaerobes Clostridium perfringens", "tumorigenesi", "tumor", "CDX 2P instability", "adenomatous polyposis coli", "CDX 2P mice", "drinking water influence"], "article_id"=>1486830, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Tatsunari Sasada", "Takao Hinoi", "Yasufumi Saito", "Tomohiro Adachi", "Yuji Takakura", "Yasuo Kawaguchi", "Yusuke Sotomaru", "Kazuhiro Sentani", "Naohide Oue", "Wataru Yasui", "Hideki Ohdan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132435.g002", "stats"=>{"downloads"=>1, "page_views"=>53, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Polyp_number_and_volume_in_the_colon_cecum_and_small_intestine_/1486830", "title"=>"Polyp number and volume in the colon, cecum, and small intestine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-17 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2180429"], "description"=>"<p>Tumors from <i>CDX2P9</i>.<i>5-G19Cre;Apc</i><sup><i>flox/flox</i></sup> mice showed a hypermutable phenotype (arrowhead and black bar) for two (<i>D7Mit91</i> and <i>GA29)</i> of four markers investigated, suggesting that tumor development occurs via MSI. The 600 LIZ size standard (Eurofins GeneScan, Frieburg, Germany) was used as a marker for sizing DNA fragments.</p>", "links"=>[], "tags"=>["cpc", "CDX 2P", "knockout mouse models", "colon polyp formation", "colorectal cancer", "Chlorinated Water Modulates", "chlorine", "nls", "chlorinated drinking water", "anaerobes Clostridium perfringens", "tumorigenesi", "tumor", "CDX 2P instability", "adenomatous polyposis coli", "CDX 2P mice", "drinking water influence"], "article_id"=>1486831, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Tatsunari Sasada", "Takao Hinoi", "Yasufumi Saito", "Tomohiro Adachi", "Yuji Takakura", "Yasuo Kawaguchi", "Yusuke Sotomaru", "Kazuhiro Sentani", "Naohide Oue", "Wataru Yasui", "Hideki Ohdan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132435.g003", "stats"=>{"downloads"=>3, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MSI_in_tumors_from_CPC_Apc_and_CDX2P9_5_G19Cre_Apc_flox_flox_mice_/1486831", "title"=>"MSI in tumors from <i>CPC;Apc</i> and <i>CDX2P9</i>.<i>5-G19Cre;Apc</i><sup><i>flox/flox</i></sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-17 03:10:59"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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