title: Heterocyclic aromatic amines and their contribution to the bacterial mutagenicity of the particulate phase of cigarette smoke.
abstract: Heterocyclic aromatic amines (HAAs) rank among the strongest known mutagens. Approximately 30 HAAs have been found in cooked foods (broiled, fried, and grilled) and several HAAs have been characterized as animal carcinogens. Nine HAAs have also been reported to be constituents of cigarette smoke (CS) raising concerns that HAAs might contribute significantly to the known carcinogenicity of CS. As HAAs are found predominantly in the total particulate matter (TPM) of CS, an improved method for the quantification of HAAs in TPM is reported allowing detection and quantification of 8 HAAs in a single run. The mutagenic potency of these HAAs and that of TPM from the reference cigarette 2R4F was determined in the Salmonella Reverse Mutation Assay (Ames assay) with tester strain TA98 and a metabolic activation system. The 8 HAAs, when applied together in the Ames assay, showed a clear sub-additive response. Likewise, the combination of HAAs and TPM, if at all, gave rise to a slight sub-additive response. In both cases, however, the sub-additive response in the Ames assay was observed at HAA doses that are far above the amounts found in CS. The contribution of the individual HAAs to the total mutagenic activity of TPM was calculated and experimentally confirmed to be approximately 1% of the total mutagenic activity. Thus, HAAs do not contribute significantly to the bacterial in vitro mutagenicity of CS TPM.
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Rue des Usines 90, 2000 Neuchâtel, Switzerland.
authors.forename: Ewald
authors.initials: E
authors.lastname: Roemer
authors.affiliation: Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Fuggerstr. 3, 51149 Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meisgen
authors.affiliation: Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Fuggerstr. 3, 51149 Cologne, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Diekmann
authors.affiliation: Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Fuggerstr. 3, 51149 Cologne, Germany.
authors.forename: Lynda
authors.initials: L
authors.lastname: Conroy
authors.affiliation: Philip Morris Products S.A., Philip Morris International R&D, Rue des Usines 90, 2000 Neuchâtel, Switzerland. Electronic address: regina.stabbert@pmi.com.
authors.forename: Regina
authors.initials: R
authors.lastname: Stabbert
mesh_terms: D000588:Amines / Q000737:chemistry / Q000633:toxicity*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009154:Mutation; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D012475:Salmonella / Q000187:drug effects* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000588:Amines; D006571:Heterocyclic Compounds; D009153:Mutagens; D052638:Particulate Matter
keywords: Bacterial mutagenicity; Cigarette smoke; Heterocyclic aromatic amines