Potent promoting activity of dimethylitaconate on gastric carcinogenesis induced by N-methylnitrosourea.
Dimethylitaconate (DMI) is one of phase II enzyme inducers suggesting a candidate for a tumor inhibitor. We tested the modifying effect of DMI on post-initiation stage of MNU induced gastric carcinogenesis in male Fischer 344 rats. Groups I and II administered N-methylnitrosourea (MNU) at a concentration of 100 ppm in the drinking water for 15 weeks. Group II was treated 0.5% DMI in the drinking water for 37 weeks after the MNU treatment. Groups III and IV were DMI alone and untreated control, respectively. DMI-treated animals showed hyperplastic changes in gastric epithelium and the incidence was 40% in the DMI alone group. MNU combined with DMI significantly increased the adenoma incidence compared with MNU alone group (P < 0.05). The concomitant administration of DMI showed a significant increase of adenocarcinoma incidence, which was 95% (P < 0.005) compared with MNU alone group (11.8%). The replicative DNA synthesis and the labelling index of bromodeoxyuridine, which are the indicators of proliferating activity, were increased in the stomach of DMI-treated rats compared with untreated control (P < 0.001 and P < 0.005, respectively). These results suggested that DMI has potent promoting potential in the post-initiation stage of gastric carcinogenesis of rats and its mechanisms are probably involved in the induction of cell proliferation including replicative DNA synthesis.
Lee
Y S
YS
Department of Pathology, Korea Cancer Center Hospital, Seoul.
Jang
J J
JJ
D000230:Adenocarcinoma / Q000139:chemically induced*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D008770:Methylnitrosourea / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced*; D013386:Succinates / Q000494:pharmacology*
D002273:Carcinogens; D013386:Succinates; D008770:Methylnitrosourea; C005229:itaconic acid