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 300 mg/kg of lycopene and/or synbiotic (Bifidobacterium lactis plus oligofructose/inulin) or their combination 2 weeks 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. (C) 2009 Elsevier Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)