Chemopreventive effects of bovine lactoferrin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis.
Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat bladder medium-term bioassay. In experiment 1, a total of 80 F344 male rats, 6 weeks old, were divided into 5 groups. Groups 1 and 2 were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 8 weeks and after a 1-week interval, received dietary supplementation with 2% and 0.2% bLF, respectively. Group 3 received 0.05% BBN for 8 weeks and then no treatment. Group 4 was administered 2% bLF alone from week 9, without prior carcinogen exposure. Group 5 was maintained without any treatment throughout the experiment. All rats were killed at the end of week 36. Group 1 demonstrated a significantly decreased multiplicity of the bladder tumors (carcinomas and papillomas) as compared with group 3. Maximum cut surface areas of bladder tumors were also significantly decreased in groups 1 and 2 compared with group 3. No bladder tumors were observed in groups 4 or 5. In experiment 2, a total of 60 rats were divided into two groups (30 rats each); both were treated with 0.05% BBN for 4 weeks and after a 1-week interval, one received 2% bLF (group 1) and the other, basal diet (group 2) for 4 weeks. Group 1 demonstrated a tendency for decrease of the 5-bromo-2'-deoxyuridine (BrdU) labeling index. bLF was detected in the urine of rats fed bLF by ELISA as well as western blot analysis. The findings indicate that 2% bLF can inhibit BBN-induced rat bladder carcinogenesis, and that this may be due to bLF in the urine.
Masuda
C
C
Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
Wanibuchi
H
H
Sekine
K
K
Yano
Y
Y
Otani
S
S
Kishimoto
T
T
Tsuda
H
H
Fukushima
S
S
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D002417:Cattle; D002712:Chlorides / Q000652:urine; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007781:Lactoferrin / Q000627:therapeutic use*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011188:Potassium / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000652:urine; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D016588:Anticarcinogenic Agents; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D002712:Chlorides; D007781:Lactoferrin; D009955:Ornithine Decarboxylase; D011188:Potassium; D012964:Sodium; D000099228:Diamine N-Acetyltransferase