Abstract
Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.Trial RegistrationClinicalTrials.gov NCT00340743.
Highlights
Colorectal cancer is the fourth most common cancer worldwide [1], and consumption of red and processed meat has been associated with increased risk of and mortality from this cancer [2,3]
heterocyclic amines (HCAs) are mutagenic and carcinogenic compounds formed through pyrolysis of aromatic amino acids and creatinine in meats cooked at high temperature, by pan-frying [5]
In animals, and in humans indicate that various dietary components, such as cruciferous vegetables, chlorophyllin (CHL), and fermented milk products, may modulate cancer risks associated with meat consumption in general and the mutagenic and carcinogenic effects of HCAs [6,7,8,9,10,11]
Summary
Colorectal cancer is the fourth most common cancer worldwide [1], and consumption of red and processed meat has been associated with increased risk of and mortality from this cancer [2,3]. Consumption of red meat and meat cooked at high temperature containing elevated levels of heterocyclic amines (HCAs) is associated with increased risk of colorectal adenoma [4]. HCAs are mutagenic and carcinogenic compounds formed through pyrolysis of aromatic amino acids and creatinine in meats cooked at high temperature, by pan-frying [5]. In animals, and in humans indicate that various dietary components, such as cruciferous vegetables, chlorophyllin (CHL), and fermented milk products, may modulate cancer risks associated with meat consumption in general and the mutagenic and carcinogenic effects of HCAs [6,7,8,9,10,11]. Glucosinolates and isothiocyanates in cruciferous vegetables inhibit HCA-induced genotoxicity by several mechanisms, including inhibition of phase I metabolizing enzymes, induction of phase II detoxification enzymes, and apoptosis [6]
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