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)

Cancer Lett. 1999 Apr 1;137(2):193-200. doi: 10.1016/s0304-3835(98)00358-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carcinogenicity Tests
  • Carcinogens
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / enzymology
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / enzymology
  • Male
  • Maleates / pharmacology*
  • Methylnitronitrosoguanidine / toxicity*
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • Papilloma / chemically induced
  • Papilloma / enzymology
  • Pepsinogen A / metabolism
  • Rats
  • Rats, Wistar
  • Saline Solution, Hypertonic / pharmacology
  • Stomach / drug effects*
  • Stomach / enzymology*
  • Stomach Neoplasms / chemically induced*
  • Stomach Neoplasms / enzymology

Substances

  • Carcinogens
  • Maleates
  • Saline Solution, Hypertonic
  • Methylnitronitrosoguanidine
  • Pepsinogen A
  • NAD(P)H Dehydrogenase (Quinone)
  • diethyl maleate