title: Inhibitory effect of dietary monoglucosylceramide 1-O-beta-glucosyl-N-2'-hydroxyarachidoyl-4,8-sphingadienine on two different categories of colon preneoplastic lesions induced by 1,2-dimethylhydrazine in F344 rats.
abstract: Sphingolipids display a wide spectrum of biological activities, including cell growth, differentiation and apoptosis. However, precise mechanisms by which these compounds exert anticancer or cancer-preventive effects are not known. In the present study, we evaluated the preventive efficacy of enriched dietary monoglucosylceramide 1-O-beta-glucosyl-N-2'-hydroxyarachidoyl-4,8-sphingadienine (G(1)CM) on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) and beta-catenin-accumulated crypt (BCAC) formation in F344 rats during initiation stage. We also examined whether G(1)CM affects cell proliferation and apoptosis in these lesions. Pure G(1)CM was isolated from rice bran. Forty-two rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneous injections of DMH (40 mg/kg body weight) once a week for 2 weeks. One week before the first injection of DMH, rats in groups 2 and 3 were fed a diet containing 200 and 1,000 p.p.m. G(1)CM, respectively, for 5 weeks. Rats in group 4 were fed a diet containing 1,000 p.p.m. G(1)CM. Rats in group 5 were given the basal diet alone and served as untreated controls. The experiment was terminated 5 weeks after the start. Dietary G(1)CM at both doses (groups 2 and 3) significantly inhibited the induction of ACF and BCAC (P<0.001) when compared to group 1 treated with DMH alone. In groups 2 and 3, the proliferating cell nuclear antigen labeling indices of epithelial cells in ACF and BCAC were also lower than in group 1 (P<0.0001 for ACF, P<0.05 for BCAC). These results, that dietary G(1)CM has possible chemopreventive effects in the present short-term colon carcinogenesis bioassays, suggest that longer exposure may cause suppression of tumor development.
authors.affiliation: Tumor Pathology, University of the Ryukyus Faculty of Medicine, 207 Uehara Nishihara-cho, Okinawa 903-0215, Japan.
authors.forename: Morihiko
authors.initials: M
authors.lastname: Inamine
authors.forename: Masumi
authors.initials: M
authors.lastname: Suzui
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Morioka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kinjo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kaneshiro
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sugishita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okada
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimi
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004032:Diet; D005963:Glucosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D012275:Oryza; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D013107:Sphingolipids / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C508503:1-O-beta-glucosyl-N-2'-hydroxyarachidoyl-4,8-sphingadienine; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D005963:Glucosylceramides; D013107:Sphingolipids; D019813:1,2-Dimethylhydrazine