Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries.
Fruit and vegetable consumption has consistently been associated with decreased risk of a number of aerodigestive tract cancers, including esophageal cancer. We have taken a "food-based" chemopreventive approach to evaluate the inhibitory potential of lyophilized black raspberries (LBRs) against N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in the F344 rat, during initiation and postinitiation phases of carcinogenesis. Anti-initiation studies included a 30-week tumorigenicity bioassay, quantification of DNA adducts, and NMBA metabolism study. Feeding 5 and 10% LBRs, for 2 weeks prior to NMBA treatment (0.25 mg/kg, weekly for 15 weeks) and throughout a 30-week bioassay, significantly reduced tumor multiplicity (39 and 49%, respectively). In a short-term bioassay, 5 and 10% LBRs inhibited formation of the promutagenic adduct O(6)-methylguanine (O(6)-meGua) by 73 and 80%, respectively, after a single dose of NMBA at 0.25 mg/kg. Feeding 5% LBRs also significantly inhibited adduct formation (64%) after NMBA administration at 0.50 mg/kg. The postinitiation inhibitory potential of berries was evaluated in a second bioassay with sacrifices at 15, 25, and 35 weeks. Administration of LBRs began after NMBA treatment (0.25 mg/kg, three times per week for 5 weeks). LBRs inhibited tumor progression as evidenced by significant reductions in the formation of preneoplastic esophageal lesions, decreased tumor incidence and multiplicity, and reduced cellular proliferation. At 25 weeks, both 5 and 10% LBRs significantly reduced tumor incidence (54 and 46%, respectively), tumor multiplicity (62 and 43%, respectively), proliferation rates, and preneoplastic lesion development. Yet, at 35 weeks, only 5% LBRs significantly reduced tumor incidence and multiplicity, proliferation indices and preneoplastic lesion formation. In conclusion, dietary administration of LBRs inhibited events associated with both the initiation and promotion/progression stages of carcinogenesis, which is promising considering the limited number of chemopreventives with this potential.
Kresty
L A
LA
Division of Environmental Health Sciences, School of Public Health, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Morse
M A
MA
Morgan
C
C
Carlton
P S
PS
Lu
J
J
Gupta
A
A
Blackwood
M
M
Stoner
G D
GD
D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D018890:Chemoprevention / Q000379:methods; D018736:DNA Adducts / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004032:Diet; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D004610:Ellagic Acid / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005612:Freeze Drying; D005638:Fruit; D006147:Guanine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D018736:DNA Adducts; D018809:Proliferating Cell Nuclear Antigen; D004610:Ellagic Acid; D006147:Guanine; C014707:nitrosobenzylmethylamine; C008449:O-(6)-methylguanine; D004128:Dimethylnitrosamine