Abstract B46: Dietary acrylamide differentially modulates azoxymethane-induced F344 rat colon tumor formation and ectopic growth of human colon tumor cells in nude (nu/nu) mice

Abstract

Abstract Acrylamide, a known rodent and a possible human carcinogen is ubiquitously formed in foods at high temperature. We earlier reported that dietary acrylamide at doses known to cause rodent tumors, did not increase the formation of azoxymethane (AOM)-induced colon aberrant crypt foci (ACF), putative precancerous lesions. On the contrary, we observed a significant decrease in ACF in rats receiving acrylamide at 10 and 50 mg/kg diet and a trend to increase ACF at the lowest dose (5mg acrylamide/kg diet) tested. In this study using two rodent models, we assessed if dietary acrylamide, at levels reflecting those in popular human foods, modulated colon tumor formation and progression. In Experiment-1, 4 groups of weanling male F344 rats received AIN-93G diets with acrylamide at 0.5, 1.0 or 2.0 mg/kg diet or without (0 mg/kg diet, control). After two weeks, rats in each diet group received either two weekly s.c. injections of AOM or saline. All rats were on the experimental diets ad libitum for 20 weeks post AOM/saline injections after which they were killed and their colons assessed for tumors. In Experiment-2, athymic nude (nu/nu) mice were s.c. injected with HT-29 human colon adenocarcinoma cells and tumors were allowed to grow for 3 weeks after which they received one of the 4 experimental diets; tumor growth was monitored bi-weekly and mice were killed 4 weeks after. None of the saline-injected rats had tumors in their colon. 23 rats that received acrylamide had blood in their stool at 19 weeks post-AOM injections, and hence the study was stopped in a timely manner at 20 weeks post-AOM injections. The colon tumor incidence was 54.2% in the control group and 66.67% in the highest acrylamide-treated group (2 mg/kg diet). Tumor multiplicity was similar across all diet groups. However, tumor size and burden were higher in the group that received 2 mg/kg acrylamide by comparison to the control. These results suggest acrylamide by itself is not a “carcinogen” at upper exposure levels commonly seen in popular foods, but acts as a “co-carcinogen” at the highest tested dose by exacerbating the risk of developing colon tumors by a known colon-specific carcinogen AOM. The nude mice study indicated no differences in ectopic human colon tumor growth between acrylamide-treated and control mice suggesting that acrylamide at the levels tested does not aid in the progression of established human tumors in this experimental model. Our data provides characterization of acrylamide as a possible colon cancer promoter in association with a known and possibly other environmental tumor initiators/promoters. This additional information will be useful in defining the health risks of acrylamide when exposed through the diet, and will assist regulators in developing a better understanding of the relevance to humans. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B46.