Inhibition of PhIP-induced mammary carcinogenesis in female rats by ingestion of freeze-dried beer.
This study evaluated the modulating effect of non-alcoholic constituents of beer on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis. Female Sprague-Dawley (SD) rats at 6 weeks of age were divided into four groups (n=26-30) and fed either a high fat diet or high fat diets containing 1, 2 or 4% freeze-dried beer (FD beer). One week after the start of feeding, rats received PhIP at a dose of 85 mg/kg by gavage four times weekly for 2 weeks. There were no differences in the body weights or diet intakes of rats between the control and the experimental groups. Weekly observation of palpable tumors indicated that tumor incidence and tumor multiplicity in the 2 and 4% FD beer groups were lower than in the control group throughout the experiment. Neoplastic lesions were pathologically examined at the end of the 22-weeks experiment. Tumor development was inhibited by FD beer intake in a dose-dependent manner. Tumor incidence (38.5%) and tumor multiplicity (0.8+/-0.4) for the group fed with a diet containing 4% FD were significantly reduced as compared with the control group (73.3% and 1.8+/-0.7). Supplementation with FD beer for 3 weeks together with the PhIP treatments resulted in increased liver GST activity, decreased liver CYP1A2 activity and a decrease in the number of DNA adducts in the mammary tissue, though these values were not significant. In conclusion, our results suggest that intake of FD beer may reduce the risk of carcinogenesis caused by heterocyclic amines.
Nozawa
Hajime
H
Central Laboratories for Key Technology, Kirin Brewery Co. Ltd, 1-13-5 Fukuura, Yokohama 236-0004, Japan. h-nozawa@kirin.co.jp
Nakao
Wakako
W
Takata
Jun
J
Arimoto-Kobayashi
Sakae
S
Kondo
Keiji
K
D000818:Animals; D001515:Beer; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D018736:DNA Adducts; D004041:Dietary Fats; D019587:Dietary Supplements; D005260:Female; D005612:Freeze Drying; D005982:Glutathione Transferase / Q000378:metabolism; D007093:Imidazoles / Q000633:toxicity*; D015994:Incidence; D008099:Liver / Q000201:enzymology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D018736:DNA Adducts; D004041:Dietary Fats; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase