Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat.
A milk component, bovine lactoferrin (bLF), previously shown by us to be a strong chemopreventive of colon carcinoma development, was examined for its influence on other organs using a rat multi-organ carcinogenesis model. Male F344 rats, aged 6 weeks, were treated sequentially with diethylnitrosamine (DEN, i.p.), dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) and N-nitrosomethylbenzylamine (NMBA, s.c.) during the first 8 weeks (DDN treatment), and then bLF was administered in the basal diet, at a dose of 2, 0.2, 0.02 or 0.002%. Other groups were given DDN treatment or bLF alone as controls. All surviving animals were killed at week 41, and major organs were examined histopathologically for neoplastic lesions. In the esophagus, a tendency for reduction in development of papillomas was evident in the bLF-treated animals, along with a significant suppression of relatively large-sized papillomas (more than 50 mm3 volume) at the 0.2% dose (P<0.05, 11% of the control). The multiplicity of tumors (adenomas and carcinomas) in the lung was also decreased in animals fed 0.02% bLF (1.98+/-0.41 per cm2 lung tissue section, P<0.05) compared to the control group (3.48+/-0.33). No enhancing or inhibitory effects of bLF on tumor development in other organs were noted. The present results indicate that bLF exerts chemopreventive effects in the esophagus and lung in addition to the colon.
Ushida
Y
Y
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Tokyo.
Sekine
K
K
Kuhara
T
T
Takasuka
N
N
Iigo
M
M
Maeda
M
M
Tsuda
H
H
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015994:Incidence; D007781:Lactoferrin / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007781:Lactoferrin