Lack of modification of rat hepatocarcinogenesis by fernane-type triterpenoids, isolated from a Euphorbia genus.
Inhibitors of topoisomerases, enzymes that produce an unusual type of DNA damage, are considered as antitumor agents. Recently it has been reported that the fernane-type triterpenoid EC-2 and its hydroxyl derivative, isolated from Euphorbia, are potent topoisomerase II inhibitors. In this study, the modifying effects of EC-2 and EC-4 on the development of putative preneoplastic lesions, glutathione S-transferase placental form (GST-P)-positive foci, in the liver of rats were investigated using a medium-term bioassay system. Fisher 344 male, 6-week-old rats were given a single intraperitoneal injection (200 mg/kg b.w.) of diethylnitrosamine or saline at the beginning of the experiment and subjected to 2/3 partial hepatectomy at the 3rd week. The test compounds were administered five times/week by i.g. gavage at a dose of 1 mg/kg b.w. from 2 to 8 weeks. Quantitation of the numbers and areas per cm(2) of induced GST-P positive foci did not demonstrated any significant differences among the groups and no variation in cell proliferation as indicated by 5-bromo- 2'-deoxyuridine (BrdU) labeling. Our results suggest that EC-2 and EC-4 have no modifying effects on rat hepatocarcinogenesis.
Karim
Rezaul
R
Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka, Japan.
Iwai
Shuji
S
Morimura
Keiichirou
K
Wanibuchi
Hideki
H
Tanaka
Reiko
R
Matsunaga
Shunyo
S
Yoshitake
Akira
A
Fukushima
Shoji
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D004052:Diethylnitrosamine; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000627:therapeutic use*; D028481:Euphorbia / Q000737:chemistry*; D005982:Glutathione Transferase / Q000032:analysis; D006498:Hepatectomy; D007527:Isoenzymes / Q000032:analysis; D008107:Liver Diseases / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008115:Liver Regeneration; D008297:Male; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D008517:Phytotherapy; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes / Q000302:isolation & purification / Q000627:therapeutic use*
C463379:3,4-seco-8betaH-ferna-4(23),9(11)-dien-3-oic acid; C463380:3,4-seco-oleana-4(23),18-dien-3-oic acid; D016588:Anticarcinogenic Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009363:Neoplasm Proteins; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes; D004052:Diethylnitrosamine; D005982:Glutathione Transferase