Inhibitory effects of phenolic compounds on development of naturally occurring preneoplastic hepatocytic foci in long-term feeding studies using male F344 rats.
Five phenolic compounds, namely caffeic acid, sesamol, hydroquinone, catechol, and 4-methoxyphenol, were fed to groups of 30 male F344 rats at dietary levels of 2, 2, 0.3, 0.8, and 2%, respectively, for 2 years. Retardation of body weight and elevated relative liver weights were noted for all groups. Formalin-fixed and paraffin-embedded liver tissues from rats killed terminally were cut and stained for glutathione S-transferase placental form (GST-P) and tumor growth factor alpha (TGF alpha) immunohistochemically. Numbers and areas of GST-P-positive (GST-P+) foci per unit area of liver section were measured, and the respective treated/control proportional values were calculated to be 58 and 57% for caffeic acid. 58 and 54% for sesamol, 71 and 71% for hydroquinone. 58 and 133% for catechol, and 49 and 39% for 4-methoxyphenol. These data were comparable with results obtained with medium-term liver bioassays (Ito test). However, no intergroup differences were detected with regard to quantitative findings for TGF alpha foci, which were relatively rare. Long-term inhibitory effects of phenolic compounds on liver carcinogenesis, predicted from the Ito test, were thus confirmed in the present feeding studies using quantitative analysis of immunohistochemically demonstrable GST-P+ foci as end point marker lesions.
Hagiwara
A
A
Daiyu-kai Institute of Medical Science, Ichinomiya, Japan.
Kokubo
Y
Y
Takesada
Y
Y
Tanaka
H
H
Tamano
S
S
Hirose
M
M
Shirai
T
T
Ito
N
N
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D005982:Glutathione Transferase / Q000032:analysis; D007150:Immunohistochemistry; D008099:Liver / Q000033:anatomy & histology; D008114:Liver Neoplasms, Experimental / Q000737:chemistry / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000737:chemistry / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D016211:Transforming Growth Factor alpha / Q000032:analysis
D016588:Anticarcinogenic Agents; D010636:Phenols; D016211:Transforming Growth Factor alpha; D005982:Glutathione Transferase