Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries

Cancer Res. 2001 Aug 15;61(16):6112-9.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinogens / antagonists & inhibitors
  • Carcinogens / metabolism
  • Carcinogens / toxicity
  • Chemoprevention / methods
  • DNA Adducts / antagonists & inhibitors
  • DNA Adducts / biosynthesis
  • Diet
  • Dimethylnitrosamine / analogs & derivatives
  • Dimethylnitrosamine / antagonists & inhibitors
  • Dimethylnitrosamine / metabolism
  • Dimethylnitrosamine / toxicity
  • Ellagic Acid / pharmacology
  • Esophageal Neoplasms / chemically induced
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / prevention & control*
  • Freeze Drying
  • Fruit*
  • Guanine / analogs & derivatives
  • Guanine / antagonists & inhibitors
  • Guanine / biosynthesis
  • Male
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / prevention & control
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Inbred F344

Substances

  • Carcinogens
  • DNA Adducts
  • Proliferating Cell Nuclear Antigen
  • Ellagic Acid
  • Guanine
  • nitrosobenzylmethylamine
  • O-(6)-methylguanine
  • Dimethylnitrosamine