No inhibition of urinary bladder carcinogenesis in rats with intravesical instillation of alpha-galactosylceramide.
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.
Mitsuhashi
Makoto
M
Department of Pathology, Osaka City University Medical School, Osaka 545-8585, Japan. fukuchan@med.osaka-cu.ac.jp
Wanibuchi
Hideki
H
Wei
Min
M
Doi
Ken'ichro
K
Morimura
Keiichirou
K
Masuda
Chikayoshi
C
Wada
Seiji
S
Nakatani
Tatsuya
T
Kakizoe
Tadao
T
Fukushima
Shoji
S
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
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D005699:Galactosylceramides; C103873:KRN 7000