Inhibition of the development of hepatocellular carcinomas by phenyl N-tert-butyl nitrone in rats fed with a choline-deficient, L-amino acid-defined diet.
Effects of phenyl N-tert-butyl nitrone (PBN), a spin-trapping agent, on the development of frank cancers were examined in male Wistar rats fed with a choline-deficient, l-amino acid-defined (CDAA) diet for 70 weeks. PBN (0.065% in the drinking water) reduced incidences, multiplicities and possibly sizes of both hepatocellular adenomas and carcinomas when administered for all 70 weeks or only for the first 26 weeks, and those of carcinomas but not adenomas, when administered only for the last 44 weeks. These results indicate that PBN can prevent the development of frank HCCs in the CDAA diet model. The anti-carcinogenic effect of PBN may be ascribed to the prevention of both the development of HCAs and their malignant conversion to HCCs. If such findings can be generalized, PBN may be able to serve as a good tool to investigate molecular mechanisms underlying carcinogenic processes.
Nakae
Dai
D
Department of Pathology, Sasaki Institute, Sasaki Foundation, 2-2 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan. dai.nakae@sasaki.or.jp
Uematsu
Fumiyuki
F
Kishida
Hideki
H
Kusuoka
Osamu
O
Katsuda
Shin-Ichi
S
Yoshida
Midori
M
Takahashi
Masakazu
M
Maekawa
Akihiko
A
Denda
Ayumi
A
Konishi
Yoichi
Y
Kotake
Yashige
Y
Floyd
Robert A
RA
D000236:Adenoma / Q000209:etiology / Q000517:prevention & control*; D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control*; D002796:Choline Deficiency / Q000150:complications*; D003497:Cyclic N-Oxides; D004032:Diet; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009589:Nitrogen Oxides / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014867:Water
D000596:Amino Acids; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D014867:Water; C029217:phenyl-N-tert-butylnitrone