| AUTHOR: |
|
Tsuda H, Uehara N, Iwahori Y, Asamoto M, Iigo M, Nagao M, Matsumoto K,
Ito M, Hirono I |
| ABSTRACT: |
|
Inhibitory effects of naturally occurring antioxidants on the
initiation stage of hepatocarcinogenesis were studied. Group 1 rats were
given a diet containing beta-carotene (beta-CT, 0.02%), alpha-tocopherol
(alpha-TP, 1.5%), glutathione (GLT, 5%), vanillin (VNL, 1%), quercetin
(QCT, 1%) or ellagic acid (ELA, 1%), or 3 doses of diallyl sulfide (DAS,
200 mg/kg, i.g.) over an 8-day period. On day 7, the animals received a
single dose of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ, 100 mg/kg,
i.g.), 12 h after two-thirds partial hepatectomy for initiation and 2
weeks thereafter, were placed on promotion regimen comprising
phenobarbital (0.05% in diet) and a single dose of D-galactosamine (100
mg/kg, i.p.). Groups 2 and 3 were treated as described for Group 1, but
without test material or IQ, respectively. Survivors were killed at week
11 and antioxidant influence was assessed by comparing values for
preneoplastic glutathione S-transferase placental form-positive (GST-P+)
foci between Groups 1 and 2. All lesions larger than 70 microns in
diameter consisting of approximately 5 cells in cross section were
counted. Numbers of GST-P+ foci/cm2 in Group 1 were: beta-CT, 7.99;
alpha-TP, 8.21; GLT, 9.71; DAS, 10.37; VNL, 10.57; QCT, 11.1; ELA, 12.5 (n
= 11-15). All, except ELA, showed a significant decrease as compared with
the Group 2 value of 14.54 (n = 15). Only beta-CT showed a significant
decrease for the area value. This is the first report to show that
beta-CT, alpha-TP, GLT, DAS, VNL, QCT exert inhibitory effects on
initiation of hepatocarcinogenesis by the food carcinogen IQ, suggesting
that these antioxidants might find application as chemopreventive agents.
Furthermore, the current protocol proved practical for the assessment of
chemopreventive agents within 11 weeks, a relatively short period. |