Inhibition of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus by dietary freeze-dried strawberries.
In the present study, we examined the ability of dietary freeze-dried strawberries to inhibit N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus. Initially, we conducted a bioassay to determine the effects of dietary freeze-dried strawberries on esophageal tumor development. Two weeks prior to NMBA treatment, animals were placed on a control diet or diets containing 5 and 10% freeze-dried strawberries. NMBA treatment was once per week for 15 weeks. At 30 weeks, 5 and 10% freeze-dried strawberries in the diet caused significant reductions in esophageal tumor multiplicity of 24 and 56%, respectively. Based on these results, we conducted studies to determine potential mechanisms by which freeze-dried strawberries inhibit tumorigenesis. In a short-term bioassay, we evaluated the effects of dietary freeze-dried strawberries on the formation of O6-methylguanine in the rat esophagus. Animals were placed on control diet or diets containing 5 and 10% freeze-dried strawberries for two weeks. At the end of this period, animals received a single subcutaneous dose of NMBA and were killed 24 h later. A significant decrease in O6-methylguanine levels was observed in the esophageal DNA of animals fed strawberries, suggesting that one or more components in strawberries influence the metabolism of NMBA to DNA-damaging species. Finally, in order to evaluate post-initiation effects, we conducted a study where freeze-dried strawberries were administered in the diet only following NMBA treatment. Animals were placed on control diet and dosed with NMBA three times per week for 5 weeks. Immediately following NMBA treatment, animals were placed on control diet or diets containing 5 and 10% freeze-dried strawberries. At 25 weeks, 5 and 10% freeze-dried strawberries in the diet significantly reduced tumor multiplicity by 38 and 31%, respectively. Our data suggest that dietary freeze-dried strawberries effectively inhibit NMBA-induced tumorigenesis in the rat esophagus.
Division of Environmental Health Sciences, The Ohio State University School of Public Health and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Room 1148, 300 West 10th Avenue, Columbus, OH 43210, USA.
P S
PS
Carlton
L A
LA
Kresty
J C
JC
Siglin
M A
MA
Morse
J
J
Lu
C
C
Morgan
G D
GD
Stoner
D000818:Animals; D016588:Anticarcinogenic Agents; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D005638:Fruit; D008297:Male; D051381:Rats
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018736:DNA Adducts; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine