title: Cytotoxic and mutagenic effects of tobacco-borne free fatty acids.
abstract: Tobacco smoke contains substances capable of binding iron in an aqueous medium and transferring the metal into both organic solvents and intact mammalian red cells. This iron-binding activity is due to free fatty acids which are abundant in tobacco smoke and form 2:1 (free fatty acid:iron) chelates with ferrous iron. These earlier observations suggested that smoke-borne free fatty acids and the associated delocalization of iron within the lung might contribute to both the chronic pulmonary inflammation and the carcinogenesis associated with smoking. We now report that micromolar concentrations of iron or free fatty acid are not toxic to cultured human lung fibroblasts. However, when combined, the same low concentrations of iron and free fatty acid exert synergistic toxicity. Furthermore, the combination of free fatty acid and iron is highly mutagenic, inducing almost as many selectable mutations in the gene for hypoxanthine/guanine phosphoribosyl transferase as does benzo[a]pyrenediolepoxide, a class I carcinogen generated from benzo[a]pyrene present in cigarette smoke. The combination of free fatty acid and iron also promotes transformation of NIH 3T3 cells into an anchorage-independent phenotype. We conclude that free fatty acids in tobacco smoke may be important contributors to both the pulmonary damage and the carcinogenesis associated with smoking.
authors.affiliation: Molecular Targets Group, J. G. Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Gao
authors.forename: Mingwei
authors.initials: M
authors.lastname: Qian
authors.forename: Jian Li
authors.initials: JL
authors.lastname: Campian
authors.forename: Denise R
authors.initials: DR
authors.lastname: Clark
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Burke
authors.forename: John W
authors.initials: JW
authors.lastname: Eaton
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McGregor
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000633:toxicity*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007501:Iron / Q000633:toxicity*; D008168:Lung / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D041681:NIH 3T3 Cells / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D014026:Nicotiana
chemical_list: D005230:Fatty Acids, Nonesterified; D009153:Mutagens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D007501:Iron; D007041:Hypoxanthine Phosphoribosyltransferase