The mutagenic activity of select azo compounds in MutaMouse target tissues in vivo and primary hepatocytes in vitro

Publication date: Available online 13 June 2019Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Julie A. Cox, Paul A. WhiteAbstractThe mutagenicity of Direct Black 38, Sudan I, and Para Red were evaluated in the in vivo MutaMouse assay and the in vitro MutaMouse primary hepatocyte (PH) assay. Direct Black 38 is an International Agency for Research on Cancer (IARC) Group 1 carcinogen and a prototypical benzidine-based azo compound that requires azo-reduction to yield a DNA-reactive metabolite. Sudan I and Para Red are structurally related azo compounds that have been detected as illegal contaminants in foods. Sudan I is an in vivo mutagen, and both it and Para Red are known to be mutagenic in vitro. Sudan I is oxidized by hepatic and/or bladder enzymes to yield a mutagenic metabolite, but little is known about Para Red. In the present study, Direct Black 38 elicited a significant mutagenic response in the bone marrow, glandular stomach, small intestine and colon in vivo, and in PHs in vitro. Sudan I elicited a weak positive response in the bone marrow and a marginally significant treatment effect in the bladder (p = 0.059); it did not elicit a significant response in PHs in vitro. Para Red elicited a positive response in the colon, as well as in PHs in vitro, albeit at a cytotoxic concentration. The findings are well aligned with the known mechanisms of action of Direct Black 38 and Sudan I; they suggest that intestinal azo-reduction pla...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research