Suppression of azoxymethane-induced colon carcinogenesis in male F344 rats by mandarin juices rich in beta-cryptoxanthin and hesperidin.
We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes. In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of 69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5 administration significantly reduced the frequency of colonic carcinoma [MJ: 35% (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15% (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47% reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5: 0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These findings might suggest effective chemopreventive ability of MJs, especially MJ5, in colon tumorigenesis.
Tanaka
T
T
Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. takutt@kanazawa-med.ac.jp
Kohno
H
H
Murakami
M
M
Shimada
R
R
Kagami
S
S
Sumida
T
T
Azuma
Y
Y
Ogawa
H
H
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane; D001628:Beverages; D002273:Carcinogens; D002957:Citrus; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D065366:Cryptoxanthins; D019938:Cyclin D1 / Q000096:biosynthesis; D006569:Hesperidin / Q000008:administration & dosage*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D024341:Xanthophylls; D019207:beta Carotene / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065366:Cryptoxanthins; D018809:Proliferating Cell Nuclear Antigen; D024341:Xanthophylls; D019207:beta Carotene; D019938:Cyclin D1; D006569:Hesperidin; D001397:Azoxymethane