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.
Department of Pathology, Korea Cancer Center Hospital, Seoul.
Y S
YS
Lee
J J
JJ
Jang
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