title: Probiotics prevent the development of 1,2-dimethylhydrazine (DMH)-induced colonic tumorigenesis through suppressed colonic mucosa cellular proliferation and increased stimulation of macrophages.
abstract: Probiotics modulate immunity and inhibit colon carcinogenesis in experimental models, but these effects largely depend on the bacterial strain, and the precise mechanisms are not well understood. Therefore, we studied the effect of  Bifidobacterium longum  and/or  Lactobacillus gasseri  on the development of 1,2-dimethylhydrazine (DMH)-induced colonic precancerous lesions and tumors in mice while delineating the possible mechanisms involved. The results suggest that dietary consumption of probiotics (B. longum and L. gasseri) resulted in a significant inhibition of DMH-induced aberrant crypt foci (ACF) formation in male ICR mice. Long-term (24 weeks) dietary consumption of probiotics resulted in a reduction of colon tumor multiplicity and the size of the tumors. Administration of B. longum and L. gasseri suppressed the rate of colonic mucosa cellular proliferation in a manner correlating with the inhibition of tumor induction by DMH. In addition, the phagocytic activity of peritoneal macrophages was significantly increased in the DMH-treated mice that were fed various doses of B. longum, but not with L. gasseri or combined probiotics (B. longum + L. gasseri). We also found that L. gasseri significantly increased the proliferation of RAW264.7 macrophage cells through an increase in S phase DNA synthesis, which was related to the up-regulation of proliferating cell nuclear antigen (PCNA) and cyclin A. Taken together, these results demonstrate the in vivo chemopreventive efficacy and the immune stimulating mechanisms of dietary probiotics against DMH-induced colonic tumorigenesis.
authors: Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan.
authors: Ning-Ping
authors: NP
authors: Foo
authors: Hui
authors: H
authors: Ou Yang
authors: Hsueh-Huei
authors: HH
authors: Chiu
authors: Hing-Yuen
authors: HY
authors: Chan
authors: Chii-Cherng
authors: CC
authors: Liao
authors: Chung-Keung
authors: CK
authors: Yu
authors: Ying-Jan
authors: YJ
authors: Wang
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D016588:Anticarcinogenic Agents; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000276:immunology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007070:Immunoglobulin A / Q000032:analysis; D007413:Intestinal Mucosa / Q000473:pathology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010587:Phagocytosis / Q000187:drug effects; D019936:Probiotics / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D018797:Cell Cycle Proteins; D007070:Immunoglobulin A; D019813:1,2-Dimethylhydrazine