Inflammation-associated genes as potential molecular targets for dietary prevention of colon carcinogenesis in an AOM-DSS mouse model

A143

Inflammation plays an important role in colon carcinogenesis and can be modified by diet. To identify bioactive food components for colon cancer prevention and their molecular targets, we developed a colon carcinogenesis model using azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced FVB mice. At 6 weeks of age, mice were injected intraperitoneally with AOM (10 mg/kg body weight). Mice then received for 1 week as drinking water 0 or 1% DSS dissolved in distilled water (1 and 4 weeks after AOM injection). One week after the first DSS cycle, some mice were switched from an AIN-93G diet to one enriched with 85 mg of the garlic metabolite diallyl disulfide/kg diet. Mice were sacrificed at multiple time points to coincide with early stages of colon carcinogenesis. RNA was isolated from scraped colon tissue, and transcript levels of 84 genes involved in mediating the immune response during inflammation were measured using real-time qPCR. The AOM/DSS-induced mice showed progression through stages of colon carcinogenesis. Dietary diallyl disulfide attenuated tumor multiplicity when fed after AOM/DSS-induction. Expression of most inflammation-associated genes increased gradually with progression through stages of colon carcinogenesis and with tumor multiplicity. Dietary diallyl disulfide significantly decreased (P < 0.05) the expression of a subset of these genes, among them toll interacting protein, integrin alpha M, and tumor necrosis factor receptor superfamily 1b. Our data suggest that transcript levels of inflammation-associated genes such as toll-interacting protein provide a promising indicator of an efficacious response to dietary interventions such as diallyl disulfides and may also serve as potential molecular targets for prevention of colon carcinogenesis.