title: Is individual nasal sensitivity related to cellular metabolism of formaldehyde and susceptibility towards formaldehyde-induced genotoxicity?
abstract: Forty-one volunteers (male non-smokers, aged 32 ± 9.6yrs) were tested for susceptibility towards unspecific nasal irritation (sensitivity towards CO(2)) in order to define subgroups of hypersensitive and hyposensitive subjects. Blood samples were taken and the expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase gene (FDH, identical to alcohol dehydrogenase 5, ADH5; EC 1.2.1.46) was measured in leukocytes by quantitative real-time RT-PCR with TaqMan probes. FDH is the most important enzyme for the metabolic inactivation of FA. Blood samples were exposed to 150μM formaldehyde (FA) for 2h and the induction of DNA-protein crosslinks (DPX) in leukocytes was measured by means of a modification of the alkaline comet assay (i.e., by assessing the reduction of DNA migration induced by γ-radiation). Removal of DPX was determined by the abolition of FA-induced reduction in DNA migration within 4h after the end of the exposure. Furthermore, the induction of sister chromatid exchange (SCE) in cultured lymphocytes was studied after treatment of whole blood cultures with FA (150μM). A correlation analysis was performed for all parameters tested for the whole study group and for hypersensitive and hyposensitive subgroups. The results indicate that despite large differences in CO(2)-sensitivity, the susceptibility towards nasal irritation was not related to the induction of genotoxic effects (DPX, SCE) in peripheral blood or to the protection of blood cells against FA-induced effects (expression of FDH, repair capacity for FA-induced DPX). There was no correlation between CO(2)-sensitivity and the expression of FDH. There was also no close correlation between the various indicators of cellular sensitivity towards FA-induced genotoxic effects and no subgroups were identified with particular mutagen sensitivity towards FA.
authors.affiliation: Universität Ulm, Institut für Humangenetik, D - 89069 Ulm, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Zeller
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ulrich
authors.forename: Joerg U
authors.initials: JU
authors.lastname: Mueller
authors.forename: Clarissa
authors.initials: C
authors.lastname: Riegert
authors.forename: Simone
authors.initials: S
authors.lastname: Neuss
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Triebig
authors.forename: Günter
authors.initials: G
authors.lastname: Speit
mesh_terms: D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D001773:Blood Cells / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology; D020552:Comet Assay; D004260:DNA Repair; D005557:Formaldehyde / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*; D012854:Sister Chromatid Exchange; D014276:Trigeminal Nerve / Q000187:drug effects
chemical_list: D009153:Mutagens; D002245:Carbon Dioxide; D005557:Formaldehyde; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent