title: Dietary acrylamide does not increase colon aberrant crypt foci formation in male F344 rats.
abstract: Acrylamide, a known rodent and a probable human carcinogen, is spontaneously formed in foods cooked at high temperature. We studied the role of dietary acrylamide in modulating the early stages of colon carcinogenesis and assessed if dietary fat level was critical in altering the effects of acrylamide. Male F344 rats were subcutaneously injected with azoxymethane and were simultaneously randomized into 8 dietary groups (n=8 rats/group). Diets were based on AIN-93G semi-synthetic formula modified to contain either low fat (7% corn oil) or high fat (23.9% corn oil) and acrylamide at 0, 5, 10 or 50 mg/kg diet (wt/wt). All rats received the experimental diets ad libitum for 8 weeks, after which they were killed and their colons assessed for aberrant crypt foci (ACF), putative precancerous lesions. Irrespective of dietary fat level, rats with the highest tested dose of acrylamide (50 mg/kg diet) had significantly lower total ACF (p<0.05) and lower large ACF (those with 4 or more crypts/focus; p<0.001) compared with their respective controls (0 mg/kg diet). A significantly lower number of large ACF (p=0.046) was noted in rats treated with 10 mg/kg diet acrylamide exclusively in the high fat group, compared to the high fat control. This short-term bio-assay to test carcinogenicity of dietary acrylamide in the colon demonstrates that acrylamide, when administered through the diet at doses known to cause rat tumors, does not increase the risk of developing azoxymethane-induced precancerous lesions of the colon in rats. On the contrary, a high dose of dietary acrylamide decreased the growth of precancerous lesions in both low and high fat diet regimens in this model.
authors.affiliation: Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario, Canada. jayadev_raju@hc-sc.gc.ca
authors.forename: Jayadev
authors.initials: J
authors.lastname: Raju
authors.forename: Chandni
authors.initials: C
authors.lastname: Sondagar
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roberts
authors.forename: Syed A
authors.initials: SA
authors.lastname: Aziz
authors.forename: Don
authors.initials: D
authors.lastname: Caldwell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Vavasour
authors.forename: Rekha
authors.initials: R
authors.lastname: Mehta
mesh_terms: D058739:Aberrant Crypt Foci / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D020106:Acrylamide / Q000145:classification / Q000633:toxicity*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D014408:Biomarkers, Tumor / Q000378:metabolism; D002273:Carcinogens / Q000145:classification / Q000633:toxicity*; D053453:Caspase 9 / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003314:Corn Oil / Q000008:administration & dosage*; D004347:Drug Interactions; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D020106:Acrylamide; D003314:Corn Oil; D053453:Caspase 9; D001397:Azoxymethane