Antagonistic effect of diethylmaleate on the promotion of forestomach carcinogenesis by butylated hydroxyanisole (BHA) in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine.
The effects of diethylmaleate (DEM), previously demonstrated to inhibit butylated hydroxyanisole (BHA)-induced forestomach hyperplasia, on BHA promotion of forestomach carcinogenesis in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined. Groups of male 6-week-old F344 animals were given a single i.g. administration of 150 mg/kg body weight MNNG and starting 1 week later administered powdered diet containing 1% BHA plus 0.2% DEM, 1% BHA, 0.2% DEM or basal diet alone for 51 weeks. Further groups of rats were treated with 1% BHA plus 0.2% DEM, 1% BHA, 0.2% DEM or basal diet alone without MNNG pretreatment. Histopathological assessment of lesions at week 52 revealed enhancement of MNNG-initiated papilloma (100 versus 50%) and squamous cell carcinoma (100 versus 0%) development by BHA as compared to controls. Additional treatment with DEM, however, significantly reduced the relative incidences of carcinoma in situ (0 versus 35.7%) and squamous cell carcinoma (35.7 versus 100%), as well as BHA-induced forestomach hyperplasia with or without prior MNNG treatment. The results thus clearly demonstrate that DEM acts as a potent antagonist to BHA-promotion of rat forestomach carcinogenesis.
Hirose
M
M
First Department of Pathology, Nagoya City University, Medical School, Japan.
Kagawa
M
M
Ogawa
K
K
Yamamoto
A
A
Ito
N
N
D000818:Animals; D002083:Butylated Hydroxyanisole / Q000633:toxicity*; D003043:Cocarcinogenesis; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control
D008298:Maleates; D008769:Methylnitronitrosoguanidine; D002083:Butylated Hydroxyanisole; C014476:diethyl maleate