title: Azoxymethane-induced colon tumors and aberrant crypt foci in mice of different genetic susceptibility.
abstract: Azoxymethane (AOM) is an organotropic colon carcinogen that is commonly used to induce colon tumors in rodents. Unlike its parent compound, 1,2-dimethylhydrazine (DMH), a tumor susceptibility phenotype in inbred mice with respect to AOM has not been established. Thus, this study was undertaken to determine whether genetic susceptibility extends to this carcinogen. SWR/J, A/J (both susceptible to DMH carcinogenesis) and AKR/J (resistant) mice were treated with 10 mg/kg AOM i.p. once a week for 8 weeks. Twenty-five weeks after the initial injection, tumor yield was determined. With a single exception, only SWR/J and A/J mice developed tumors, with a distribution that was limited to the distal colon (16.3+/-1.1 and 36.4+/-2.4. respectively). The formation of aberrant crypt foci (ACF), putative preneoplastic lesions, was also assessed in whole-mount colons using Methylene Blue staining. Consistent with tumor multiplicity, the total number of ACF was highest in A/J mice, followed by SWR/J mice. In addition, A/J mice had a significantly greater number of large ACF (five or more crypts per foci) than the other strains. Despite the absence of colon tumors, however, AKR/J mice did develop a significant number of ACF. This finding suggests that ACF in resistant mice are persistent but do not progress to tumors.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs 06269-2092, USA.
authors.forename: A
authors.initials: A
authors.lastname: Papanikolaou
authors.forename: Q S
authors.initials: QS
authors.lastname: Wang
authors.forename: D A
authors.initials: DA
authors.lastname: Delker
authors.forename: D W
authors.initials: DW
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004198:Disease Susceptibility; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains; D010641:Phenotype; D011230:Precancerous Conditions / Q000139:chemically induced*; D013045:Species Specificity
chemical_list: D002273:Carcinogens; D001397:Azoxymethane