title: Colon carcinogenesis in wild type and immune compromised mice after treatment with azoxymethane, and azoxymethane with dextran sodium sulfate.
abstract: The association between inflammation and the risk of colorectal cancer (CRC) is well documented in animal models and in humans, but the mechanistic role of inflammation in CRC is less well understood. To address this question, the induction of colon tumors was evaluated in (i) wild type (WT) and athymic BALB/c mice treated with the colon carcinogen azoxymethane (AOM) as a single agent, and (ii) in an inflammation model of colon cancer employing AOM and dextran sodium sulfate (DSS) in WT, athymic, TCRβ(-/-) , TCRδ(-/-) and TCRβ(-/-) TCRδ(-/-) C57Bl/6 mice. The athymic BALB/c mice treated with only AOM developed 90% fewer tumors than the WT mice. The difference in response was not due to metabolic activation of AOM or repair of DNA adducts. In the inflammation model using a standard sequential exposure to AOM followed by DSS treatment, the tumor incidence in WT mice was 58% with 7 adenomas and 6 adenocarcinomas. In contrast, the TCRβ(-/-) , TCRδ(-/-) and TCRβ(-/-) TCRδ(-/-) C57Bl/6 mice showed adenoma incidences of 10, 33, and 11%, respectively, and none of the immune compromised mice developed adenocarcinomas. When the DSS exposure was increased and the AOM lowered, no difference was observed between WT and TCRβ(-/-) mice due to an increase in the incidence in the TCR null mice without concomitant increase in the WT mice. No tumors were observed in mice treated with AOM or DSS alone. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Whetstone
authors.affiliation: Eppley Institute for Research in Cancer, University of Nebraska Medical Center Omaha, Nebraska.
authors.forename: Uwe A
authors.initials: UA
authors.lastname: Wittel
authors.affiliation: Eppley Institute for Research in Cancer, University of Nebraska Medical Center Omaha, Nebraska.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Michels
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center Omaha, Nebraska.
authors.forename: James M
authors.initials: JM
authors.lastname: Gulizia
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Barry
authors.initials: B
authors.lastname: Gold
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000009:adverse effects*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology*; D016264:Dextran Sulfate / Q000008:administration & dosage* / Q000494:pharmacology; D016867:Immunocompromised Host; D015994:Incidence; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency
chemical_list: D011948:Receptors, Antigen, T-Cell; D016264:Dextran Sulfate; D001397:Azoxymethane
keywords: DNA methylation; azoxymethane; colorectal cancer; immune response; inflammation