Discipline: Biological Sciences
Subcategory: Cancer Research
Kayla-Marie Jones - Tuskegee University
Co-Author(s): A. Deloris Alexander, Maureen Bower, Roger Orcutt, Kathleen Hanlon, Leonard H. Billups, and David W. Threadgill
The autochthonous flora is indispensable to gastrointestinal health, which is evidenced by the fact that germ free animals are at an increased risk of morbidity and death from a variety of developmental disorders. To determine the relevance of the autochthonous gastrointestinal flora to azoxymethane (AOM)induced colorectal cancer (CRC), we subjected the specific-pathogen-free (SPF), germfree (GF) and Altered Schaedler Flora-associated (ASF) BALB/cJ and 129SvEv mice to AOM–induced CRC, for the objective of determining the role of the microflora in CRC. After a 26 week period, the product of AOM is a colon-specific tumor. We had observed that untreated SPF, ASF and GF animals do not spontaneously produce colon tumors. Histopathological exams showed tumors in AOM injected GF and ASF animals AOM–treated SPF animals did not present any tumors. After the pathological specimens were examined the GF and ASF- identified animals had high tumor incidences and tumor penetrance compared to the AOM–treated, SPF animals. There was no significant difference between GF and ASF animals in terms of tumor sizes or incidences. However, male mice had a slightly higher number of tumors and female mice exhibited slightly larger tumors.
As a result, there were no statistical differences in regards to the gender–associated tumor size, location or incidence. The 129 SvEv and BALB/cJ mouse strains were not significantly different in tumor number (P=0.1358) but were significantly different in tumor size (P=0.0015) and location (P=0.0085), with larger tumors in 129SvEv animals. Histopathologically there were more tumors in 129 SvEv mice compared to Balb/c mice, but the difference was not significant (P=0.1512). There were no tumors found in most SPF identified animals. The factors influencing tumor production included gender (P=0.0118) and cage (P=0.0153), underscoring the significant role of the environment and gender in murine tumor incidence. A high–grade of tumor incidence was associated with GF and ASF 129SvEv animals compared to BALB/cJ animals. In addition, the occurrence of malignant tumors was associated with germfree status and no malignant tumors were seen in ASF and SPF groups. In conclusion, both environment and gender play a significant role in CRC development as does host genetics.
Funder Acknowledgement(s): Supported by RCMI Grant #G12RR003059NIH, HHMI MICROBE Grant #1263207, CAENS, CVMNAH, CAS, Tuskegee University; Lineberger Comprehensive Cancer Center, National Gnotobiotic Rodent Resource Center, and the Center for Gastrointestinal Biology and Disease UNC Chapel Hill.
Faculty Advisor: A. Deloris Alexander,