Effects of lycopene, synbiotic and their association on early biomarkers of rat colon carcinogenesis

• Published in: Food and chemical toxicology 2010-03, Vol.48 (3), p.772-780
• Main Authors: Dias, Marcos C., Vieiralves, Noelle F.L., Gomes, Maria I.F.V., Salvadori, Daisy M.F., Rodrigues, Maria A.M., Barbisan, Luis F.
• Format: Article
• Language: English
• Subjects: 1,2-Dimethylhydrazine; animal models; Animals; anticarcinogenic activity; Antineoplastic Agents, Phytogenic - pharmacology; Bifidobacterium; Bifidobacterium - chemistry; Bifidobacterium animalis; Bifidobacterium lactis; Biological and medical sciences; biomarkers; Biomarkers, Tumor; Body Weight - drug effects; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens; Carotenoids - pharmacology; Chemical agents; chemoprevention; colon; Colon carcinogenesis; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colonic Neoplasms - prevention & control; colorectal neoplasms; Comet Assay; disease prevention; DNA Damage; Eating - drug effects; experimental diets; Feces - chemistry; functional foods; Gastroenterology. Liver. Pancreas. Abdomen; Immunohistochemistry; Intestinal Mucosa - pathology; Lycopene; Male; Medical sciences; Mucins - metabolism; Oligosaccharides - chemistry; Oligosaccharides - pharmacology; Paneth Cells - pathology; prebiotics; probiotics; Proliferating Cell Nuclear Antigen - metabolism; Rats; Rats, Wistar; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; symbiosis; Synbiotic; Toxicology; Tumor Suppressor Protein p53 - metabolism; Tumors; Wistar rat
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2009.12.003

This study evaluated whether a synergy exists for the combined treatment with lycopene and synbiotic on early biomarkers of colon carcinogenesis. Male Wistar rats received a diet containing 300mg/kg of lycopene and/or synbiotic (Bifidobacterium lactisplus oligofructose/inulin) or their combination 2weeks before and during carcinogen treatment with 1,2-dimethylhydrazine (DMH). Twenty-four hours after the last DMH application, the colons were processed for immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), p53 protein, hematoxylin–eosin staining for apoptosis analysis and genotoxicity of fecal water by comet assay. Eight weeks after the last DMH application, the colons were analyzed for development of classical aberrant crypt foci (ACF) and mucin-negative ACF. Treatment with lycopene, synbiotic or their combination significantly increased apoptosis, reduced the PCNA and p53 labeling indexes and the development of classical ACF and mucin-negative ACF. Furthermore, a lower genotoxicity of fecal water was also detected in the groups treated with the chemopreventive agents. An additive/synergistic effect of the combined treatment with lycopene/synbiotic was observed only for the fecal water genotoxicity and mucin-negative ACF parameters. These results indicate that an additive/synergistic of the combination of chemopreventive agents on the initiation phase of colon carcinogenesis can be detected using selective early biomarkers.