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).
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.
Kim
D J
DJ
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan. dkim0@yahoo.com
Park
C B
CB
Lee
J S
JS
Tsuda
H
H
Furihata
C
C
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000201:enzymology; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D010212:Papilloma / Q000139:chemically induced / Q000201:enzymology; D020116:Pepsinogen A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology*; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000201:enzymology
D002273:Carcinogens; D008298:Maleates; D012462:Saline Solution, Hypertonic; D008769:Methylnitronitrosoguanidine; D020116:Pepsinogen A; D016660:NAD(P)H Dehydrogenase (Quinone); C014476:diethyl maleate