title: Metabolic influences for mutation induction curves after exposure to Sudan-1 and para red.
abstract: Sudan-1 and para red are industrial dyes that have been illegally added to some foodstuffs, leading to withdrawal of the adulterated products throughout the UK since 2003. This resulted in international concern that arose because Sudan-1 is classified by International Agency for Research on Cancer as a Category 3 carcinogen. However, little is known about the dose response of this chemical at low, more biologically relevant, doses. The study therefore aimed to characterize the dose response for gene mutation and chromosomal damage induced by two azo dyes, namely Sudan-1 and para red. Gene mutations were analysed using the hypoxanthine phosphoribosyltransferase forward mutation assay and chromosomal damage was measured using the cytokinesis-blocked micronucleus assay. Two cell lines were used in these investigations. These were the AHH-1 cell line, which inducibly expresses CYP1A1, and the MCL-5 cell line derived from a subpopulation of AHH-1 cells that expresses a particularly high level of CYP1A1 activity. The MCL-5 cell line has also been transfected with two plasmids that stably express CYP1A2, CYP2A6 and CYP3A4 and all four of these CYP enzymes are known to metabolically activate Sudan-1. AHH-1 cells were used to investigate the dose response of the azo dyes, and MCL-5 cells were used to see if the dose response changed with increased metabolism. Sudan-1 induced a non-linear dose-response curve for gene mutation and chromosomal damage in AHH-1 cells. The genotoxic activity of Sudan-1 was greatly increased in MCL-5 cells. This indicated that the oxidation metabolites from Sudan-1 were both more mutagenic and more clastogenic than the parent compound. Para red also demonstrated a non-linear dose response for both gene mutation and chromosome damage in AHH-1 cells, and an increase in micronuclei induction was observed after increased oxidative metabolism in MCL-5 cells. Sudan-1 and para red are genotoxic chemicals with non-linear dose responses in AHH-1 but not in MCL-5 cells, and oxidative metabolism increases the genotoxic effect of both compounds.
authors.affiliation: Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, UK. g.johnson@swansea.ac.uk
authors.forename: George E
authors.initials: GE
authors.lastname: Johnson
authors.forename: Emma L
authors.initials: EL
authors.lastname: Quick
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Parry
authors.forename: James M
authors.initials: JM
authors.lastname: Parry
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001391:Azo Compounds / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D019457:Chromosome Breakage; D004396:Coloring Agents / Q000633:toxicity*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009284:Naphthols / Q000633:toxicity*
chemical_list: D001391:Azo Compounds; D002273:Carcinogens; D004396:Coloring Agents; D009153:Mutagens; D009284:Naphthols; C552939:para red; C024336:1-phenylazo-2-naphthol; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D019388:Cytochrome P-450 CYP1A2; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D007041:Hypoxanthine Phosphoribosyltransferase