Enhanced quinone reductase (QR) activity correlates with promotion potential of diethyl maleate (DEM) in rat forestomach and glandular stomach carcinogenesis initiated with N-methyl- N′-nitrosoguanidine (MNNG)

• Published in: Cancer letters Vol. 137; no. 2; pp. 193 - 200
• Main Authors: Kim, Dae Joong, Park, Cheol Beom, Lee, Joon Sup, Tsuda, Hiroyuki, Furihata, Chie
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.04.1999; Elsevier
• Subjects: Animals; Biological and medical sciences; Body Weight - drug effects; Carcinogenesis, carcinogens and anticarcinogens; Carcinogenicity Tests; Carcinogens; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - enzymology; Chemical agents; Diethyl maleate (DEM); Gastric Mucosa - drug effects; Gastric Mucosa - enzymology; Male; Maleates - pharmacology; Medical sciences; Methylnitronitrosoguanidine - toxicity; N-methyl- N′-nitro- N-nitrosoguanidine (MNNG); NAD(P)H Dehydrogenase (Quinone) - metabolism; Papilloma - chemically induced; Papilloma - enzymology; Pepsinogen A - metabolism; Promotive potential; Rats; Rats, Wistar; Saline Solution, Hypertonic - pharmacology; Stomach - drug effects; Stomach - enzymology; Stomach carcinogenesis; Stomach Neoplasms - chemically induced; Stomach Neoplasms - enzymology; Tumors; N-methyl- N′-nitro- N-nitrosoguanidine (MNNG); Stomach carcinogenesis; Diethyl maleate (DEM); Promotive potential; Stomach; Animal model; NAD-(P)-H dehydrogenase (quinone); Rat; Enzyme; Rodentia; Malignant tumor; Carcinogen; Vertebrata; Mammalia; Enzymatic activity; Animal; Tumor progression; Digestive diseases; Oxidoreductases; Gastric disease
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(98)00358-9

The modifying effect of diethyl maleate (DEM) on gastric tumor development was studied in rats initially given N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) and hypertonic sodium chloride (H-NaCl 10% or 5%). Groups of animals were maintained with or without a 0.2% DEM dietary supplement after treatment with MNNG and H-NaCl and sacrificed at week 20. Forestomachs and livers cytosolic NAD(P)H:quinone-acceptor oxidoreductase (QR) activity was also analyzed. The incidences of forestomach severe hyperplasias in the MNNG+H-NaCl → DEM groups were also significantly higher than in the MNNG+H-NaCl alone group ( P<0.01 and P<0.05 for 5% and 10% groups, respectively). Similarly, in the glandular stomach, the numbers of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG+H-NaCl → DEM groups were significantly increased ( P<0.01 for both concentrations). The QR activities in the groups treated with DEM showed 2- to 3-fold increases as compared with the control level. The results indicate that treatment with 0.2% DEM after MNNG initiation exerts enhancing effects on both forestomach and glandular stomach carcinogenesis. Induction of QR, a Phase II enzyme, activity in the rat stomach by DEM may be associated with promotion of stomach carcinogenesis rather than inhibition.