Biphasic modifying effect of indole-3-carbinol on diethylnitrosamine-induced preneoplastic glutathione S-transferase placental form-positive liver cell foci in Sprague-Dawley rats.
The biphasic modifying effects of indole-3-carbinol (I3C), a naturally occurring constituent of edible cruciferous vegetables, on the development of glutathione S-transferase placental form (GST-P)-positive liver cell foci were investigated by using a medium-term liver bioassay system and a newborn rat hepatocarcinogenesis system. In Experiment 1, a total of 65 male Sprague-Dawley (SD) rats were divided into 5 groups. Animals were given a single intraperitoneal (i.p.) injection of 200 mg/kg diethylnitrosamine (DEN) dissolved in saline for groups 1, 2, and 3 or a single i.p. injection of saline for groups 4 and 5. Group 1 was given the diet containing 0.25% I3C for 2 weeks prior to DEN initiation and then basal diet for 8 weeks. Group 2 was given basal diet for 4 weeks prior to and after DEN initiation and then the diet containing 0.25% I3C for 6 weeks. The rats of group 3 were placed on basal diet during the experiment. Animals of groups 4 and 5 were treated in the same manner as those of groups 1 and 2 except for injection with saline instead of DEN solution. All rats were subjected to two-thirds partial hepatectomy at week 3 and were killed at week 8 after DEN or saline injection. In Experiment 2, a total of 45 female SD rats were dosed with DEN (100 mg/kg, i.p.) or saline at 24 h after birth. After weaning at week 3, the rats were fed diet containing 0.25% I3C for 9 weeks and then were killed at week 12. In Experiment 1, preinitiation exposure to 0.25% I3C caused a significant decrease in numbers of GST-P-positive liver cell foci (P < 0.05), while postinitiation exposure to 0.25% I3C caused significant increases in both number (No./cm2) and area (mm2/cm2) of GST-P-positive liver cell foci (P < 0.05 or 0.01). In Experiment 2, the relative liver weight in the DEN + I3C group was significantly increased (P < 0.001). The numbers and areas of GST-P-positive liver cell foci in the DEN + I3C group were significantly increased as compared to the values of the DEN-alone group (P < 0.001). These results clearly demonstrated that I3C exerts a promoting effect on the postinitiation stage as well as an inhibitory effect on the preinitiation stage in the medium-term liver bioassay.
Kim
D J
DJ
Department of Pathology, National Institute of Safety Research, Seoul, Korea.
Lee
K K
KK
Han
B S
BS
Ahn
B
B
Bae
J H
JH
Jang
J J
JJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine; D004790:Enzyme Induction; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000627:therapeutic use*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000201:enzymology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D007527:Isoenzymes; D004052:Diethylnitrosamine; C016517:indole-3-carbinol; D005982:Glutathione Transferase