title: No inhibition of urinary bladder carcinogenesis in rats with intravesical instillation of alpha-galactosylceramide.
abstract: The immunostimulatory a-galactosylceramide, KRN 7000 ((2S,3S,4R)-1-O-(a-D-galactopyranosyl)-2-(N-hexacosnoylamino)-1,3,4-octadecatrienol), may be anticipated to have antitumor activity in vivo apart from any direct toxicity to cancer cells. In this experiment, inhibition of rat bladder carcinogenesis by intravesically instillated KRN7000 was investigated. Male Fischer 344 rats, 6-weeks-old at the start, were divided into 4 groups, all first receiving the carcinogen, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine, in their drinking water for 12 weeks. Then groups 1 and 2 respectively were administered 500 and 50 mg/kg of KRN7000 intravesically once weekly for 17 weeks. Group 3 similarly received only 0.3 micro/l of saline (vehicle control). Group 4 did not undergo bladder catheterization. On macroscopic examination at 30 weeks, multiplicities and sizes of bladder tumors in the KRN 7000 high and low-dose groups were not significantly different from those of the vehicle control group. Histologic examination confirmed no significant variation in incidences of carcinomas or preneoplastic lesions in the bladder among groups 1 to 4. Thus the results indicate that intravesical instillation of KRN7000 does not inhibit bladder carcinogenesis in rats.
authors.affiliation: Department of Pathology, Osaka City University Medical School, Osaka 545-8585, Japan. fukuchan@med.osaka-cu.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Ken'ichro
authors.initials: K
authors.lastname: Doi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Chikayoshi
authors.initials: C
authors.lastname: Masuda
authors.forename: Seiji
authors.initials: S
authors.lastname: Wada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Tadao
authors.initials: T
authors.lastname: Kakizoe
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000283:Administration, Intravesical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D005699:Galactosylceramides; C103873:KRN 7000