Preventive effects of chrysin on the development of azoxymethane-induced colonic aberrant crypt foci in rats.
The modifying effects of dietary feeding with chrysin (5,7-dihydroxyflavone) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effect of chrysin on mitosis and apoptosis in 'normal appearing' crypts. To induce ACF, rats were given two weekly subcutaneous injections of AOM (20 mg/kg body weight). They also received an experimental diet containing chrysin (0.001 or 0.01%) for 4 weeks, starting 1 week before the first dose of AOM. AOM exposure produced a substantial number of ACF (73+/-13/rat) at the end of the study (week 4). Dietary administration of chrysin caused significant reduction in the frequency of ACF: 0.001% chrysin, 37+/-17/rat (49% reduction, P<0.001); and 0.01% chrysin, 40+/-10/rat (45% reduction, P<0.001). In addition, chrysin administration significantly reduced the mitotic index and significantly increased the apoptotic index in 'normal appearing' crypts. These findings might suggest a possible chemopreventive activity of chrysin in the early step of colon tumorigenesis through modulation of cryptal cell proliferation activity and apoptosis.
Miyamoto
Shingo
S
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. shingo7@kanazawa-med.ac.jp
Kohno
Hiroyuki
H
Suzuki
Rikako
R
Sugie
Shigeyuki
S
Murakami
Akira
A
Ohigashi
Hajime
H
Tanaka
Takuji
T
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004032:Diet; D005419:Flavonoids / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D008938:Mitosis / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D005419:Flavonoids; C043561:chrysin; D001397:Azoxymethane