Colitis-related rat colon carcinogenesis induced by 1-hydroxyanthraquinoneand methylazoxymethanol acetate (review)

Citation
T. Tanaka et al., Colitis-related rat colon carcinogenesis induced by 1-hydroxyanthraquinoneand methylazoxymethanol acetate (review), ONCOL REP, 7(3), 2000, pp. 501-508
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
ONCOLOGY REPORTS
ISSN journal
1021-335X → ACNP
Volume
7
Issue
3
Year of publication
2000
Pages
501 - 508
Database
ISI
SICI code
1021-335X(200005/06)7:3<501:CRCCIB>2.0.ZU;2-U
Abstract
Patients with long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer (CRC) compared to the general population F or investigation of the mechanisms and prevention of UC and UC-related CRC, establishment of a promising animal model for such disease is important. 1 -Hydroxyanthraquinone (1-HAQ) present in certain medicinal plants such as R ubia tinctorum L. is a genotoxic and rodent colon carcinogen. Long-term fee ding of 1-HAQ induced hyper-cell proliferation in rat colonic crypts with u lcerative changes, crypt abscess, severe inflammation and erosion before th e occurrence of tumors, which are similar to those found in human UC. In ad dition, 1-HAQ has a synergistic effect with methylazoxymethaol (MAM) acetat e on colon carcinogenesis. The polymerase chain reaction-single strand conf ormation polymorphism analysis revealed no mutations in Ki-ras and p53 in c olonic neoplasms induced by MAM acetate + 1-HAQ, MAM acetate alone or 1-HAQ alone. Also, no mutations of APC were found in these tumors. These finding s are similar to those found in human ulcerative colitis-associated colon c ancer in contrast with sporadic colon cancers. A previous study revealed th at induced colonic tumors had beta-catenin mutation with high frequency, su ggesting tumor development by activation of the beta-catenin-Tcf signaling pathway. Increased expression in TNF-alpha and IL-1 alpha, was found in the se induced colonic neoplasms, and the expression was more remarkable in col onic mucosa of rats exposed to MAM acetate + 1-HAQ, MAM acetate or 1-HAQ wh en compared with that in untreated rats. Thus, these cytokines may act as g rowth factors in rat colon carcinogenesis by MAM acetate and 1-HAQ and the synergistic effect of 1-HAQ with MAM acetate might be related to the biolog ical effects of the cytokines expressed in the inflammatory conditions indu ced by 1-HAQ.