Ingestion of viable probiotics or prebiotics is associated with anticarcinogenic effects, one mechanism of which is the detoxification of genotoxins in the gut. This mechanism was shown experimentally in animals with use of the rat colon carcinogen 1,2-dimethylhydrazine and by determining endpoints that range from tumorigenesis to induction of DNA damage. Because of the complexity of cancer initiation, cancer progression, and the exposure of cancer in the gut, many types of interactions may be envisaged. Notably, some of our newer studies showed that short-lived metabolite mixtures isolated from milk that was fermented with strains of Lactobacillus bulgaricus and Streptococcus thermophilus are more effective in deactivating etiologic risk factors of colon carcinogenesis than are cellular components of microorganisms. Ingestion of prebiotics results in a different spectrum of fermentation products, including the production of high concentrations of short-chain fatty acids. Gut flora, especially after the ingestion of resistant starch, induces the chemopreventive enzyme glutathione transferase pi in the colon of the rat. Together, these factors lead to a reduced load of genotoxic agents in the gut and to an increased production of agents that deactivate toxic components. Butyrate is one such protective agent and is associated with lowering cancer risk. It was recently shown that buytrate may inhibit the genotoxic activity of nitrosamides and hydrogen peroxide in human colon cells. In humans, the ingestion of probiotics leads to the excretion of urine with low concentrations of components that are genotoxic in human colon cells and high concentrations of components that induce oxidized DNA bases.

A human intervention study with vegetable products has been performed in twenty three healthy, non smoking males aged 27-40. It was the aim of the study to assess whether consumption of vegetables containing different carotenoids could protect against DNA damage and oxidative DNA damage. The subjects consumed their normal diets, but abstained from vegetables high in carotenoids throughout the study period. After a 2 week depletion period, they received daily 330 ml tomato juice with 40 mg lycopene (weeks 3 and 4), 330 ml carrot juice with 22.3 mg beta-carotene and 15.7 mg alpha-carotene (weeks 5 and 6), and 10 g dried spinach powder (in water or milk) with 11.3 mg lutein (weeks 7 and 8). Blood was collected weekly and DNA damage was detected in peripheral blood lymphocytes with the 'COMET' assay. Oxidised DNA bases were detected by including an incubation step with endonuclease III. The supplementation of the diet with tomato, carrot or spinach products resulted in a significant decrease in endogenous levels of strand breaks in lymphocyte DNA. Oxidative base damage was significantly reduced during the carrot juice intervention. These findings support the hypothesis that carotenoid containing plant products exert a cancer-protective effect via a decrease in oxidative and other damage to DNA in humans.

Lactic acid-producing bacteria prevent carcinogen-induced preneoplastic lesions and tumors in rat colon. Because the mechanisms responsible for these protective effects are unknown, two strains of lactic acid bacteria, Lactobacillus delbrueckii ssp. bulgaricus 191R and Streptococcus salivarius ssp. thermophilus CH3, that are used to produce yogurt, were investigated in vitro and in vivo to elucidate their potential to deactivate carcinogens. Using the "Comet assay" to detect genetic damage, we found that L. bulgaricus 191R applied orally to rats could prevent 1, 2-dimethylhydrazine-induced DNA breaks in the colon in vivo, whereas St. thermophilus CH3 were not effective. However, in vitro, both strains prevented DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in isolated primary rat colon cells. Extracts prepared from milk fermented with St. thermophilus CH3 were as efficient in deactivating MNNG as was L-cysteine. Isolated metabolites arising from bacteria during fermentation in the colon or in milk [L(+) lactate, D(-) lactate, palmitic acid and isopalmitic acid] were not effective. We postulate that thiol-containing breakdown products of proteins, via catalysis by bacterial proteases, could be one mechanism by which MNNG or other carcinogens are deactivated in the gut lumen resulting in reduced damage to colonic mucosal cells.