title: Conjugation of 7-oxodehydroabietic acid to lysine, a haptenation mechanism for an oxidized resin acid with dermal sensitizing properties.
abstract: This article explores protein conjugation of 7-oxodehydroabietic acid, a resin acid found in both aerosol from soldering with rosin flux and in rosin solids. In a murine model, conjugation (haptenation) of resin acids to proteins is required to generate antibodies against rosin. Hydroperoxy resin acids are dermal sensitizers, with haptenation thought to occur via radical mechanisms. Dermal sensitization to 7-oxodehydroabietic acid has been observed, although no radical haptenation mechanism has been proposed to explain the sensitizing properties of this compound. Conjugation of L-lysine to 7-oxodehydroabietic acid was predicted, with a Schiff base (or imine) linkage formed between C-7 of the resin acid and a free amino group of lysine. Fast atom bombardment mass spectrometry provided evidence of the conjugate; a small peak was seen for the conjugate (M+H)+ ion in aqueous ethanol with 20 mM concentrations of the free resin and amino acids. A larger conjugate peak was observed with addition of tertiary amine as a mild basic catalyst, and the intensity of the conjugate peak exceeded that of the precursors upon replacement of the ethanol with benzene. Resin acids accumulate in the plasma membrane, a non-aqueous environment apparently conducive to conjugation of 7-oxodehydroabietic acid with lysine side chains of membrane proteins. The result would be dehydroabietic acid covalently bound to protein, which could lead to interaction with immune cells having resin acid specificity. The haptenation mechanism presented may be involved in allergic contact dermatitis and occupational asthma observed from exposure to resin acid solids and aerosols. As sampling and analytical methods have been previously demonstrated for 7-oxodehydroabietic acid, this compound may be a useful exposure marker with relevance to negative health effects such as occupational asthma.
authors.affiliation: Uniformed Services of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Smith
authors.forename: C R
authors.initials: CR
authors.lastname: Bowerbank
authors.forename: P B
authors.initials: PB
authors.lastname: Savage
authors.forename: D B
authors.initials: DB
authors.lastname: Drown
authors.forename: M L
authors.initials: ML
authors.lastname: Lee
authors.forename: W
authors.initials: W
authors.lastname: Alexander
authors.forename: W W
authors.initials: WW
authors.lastname: Jederberg
authors.forename: K
authors.initials: K
authors.lastname: Still
mesh_terms: D045784:Abietanes; D001249:Asthma / Q000139:chemically induced; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D004224:Diterpenes / Q000009:adverse effects / Q000737:chemistry*; D006241:Haptens; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D009784:Occupational Diseases / Q000139:chemically induced; D016273:Occupational Exposure / Q000009:adverse effects; D010616:Phenanthrenes / Q000009:adverse effects / Q000737:chemistry*; D012116:Resins, Plant / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D045784:Abietanes; D004224:Diterpenes; D006241:Haptens; D010616:Phenanthrenes; D012116:Resins, Plant; C095375:7-oxodehydroabietic acid; D008239:Lysine