title: Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00340743.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Shaughnessy
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Gangarosa
authors.forename: Barbara
authors.initials: B
authors.lastname: Schliebe
authors.forename: David M
authors.initials: DM
authors.lastname: Umbach
authors.forename: Zongli
authors.initials: Z
authors.lastname: Xu
authors.forename: Beth
authors.initials: B
authors.lastname: MacIntosh
authors.forename: Mark G
authors.initials: MG
authors.lastname: Knize
authors.forename: Peggy P
authors.initials: PP
authors.lastname: Matthews
authors.forename: Adam E
authors.initials: AE
authors.lastname: Swank
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: David M
authors.initials: DM
authors.lastname: DeMarini
authors.forename: Jack A
authors.initials: JA
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000588:Amines / Q000378:metabolism; D019607:Brassicaceae / Q000378:metabolism*; D002735:Chlorophyllides / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D003296:Cooking; D004249:DNA Damage; D004032:Diet; D005243:Feces; D005260:Female; D006571:Heterocyclic Compounds / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D009152:Mutagenicity Tests; D010865:Pilot Projects; D012007:Rectum / Q000187:drug effects / Q000473:pathology*; D015014:Yogurt; D055815:Young Adult
chemical_list: D000588:Amines; D002735:Chlorophyllides; D006571:Heterocyclic Compounds; C007020:chlorophyllin