title: Negligible colon cancer risk from food-borne acrylamide exposure in male F344 rats and nude (nu/nu) mice-bearing human colon tumor xenografts.
abstract: Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a "complete carcinogen", but acts as a "co-carcinogen" by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters.
authors.affiliation: Toxicology Research Division, Bureau of Chemical Safety Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Jayadev
authors.initials: J
authors.lastname: Raju
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roberts
authors.forename: Chandni
authors.initials: C
authors.lastname: Sondagar
authors.forename: Kamla
authors.initials: K
authors.lastname: Kapal
authors.forename: Syed A
authors.initials: SA
authors.lastname: Aziz
authors.forename: Don
authors.initials: D
authors.lastname: Caldwell
authors.forename: Rekha
authors.initials: R
authors.lastname: Mehta
mesh_terms: D020106:Acrylamide / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001835:Body Weight; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology*; D004032:Diet; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D047368:Tumor Burden
chemical_list: D020106:Acrylamide
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