title: Investigations of potential susceptibility toward formaldehyde-induced genotoxicity.
abstract: Blood samples were taken from three groups of volunteers (30 male smokers, 30 female non-smokers, and 30 school children) and tested for ex vivo susceptibility toward formaldehyde (FA)-induced genotoxicity. Blood samples were exposed to 150 μM FA for 2 h, and the induction of DNA-protein crosslinks (DPX) in leukocytes was measured by a modification of the alkaline comet assay (i.e., reduction of γ-irradiation induced DNA migration). Removal of DPX was determined by the abolition of FA-induced reduction in DNA migration within 4 h after the end of the exposure. Induction and persistence of FA-induced DNA lesions was also measured by the sister chromatid exchange (SCE) test with cultured lymphocytes after treatment of whole blood cultures with FA (150 μM). Furthermore, the expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5) was measured in leukocytes by quantitative real-time RT-PCR with TaqMan probes. The subjects were also analyzed for the GSTM1 and GSTT1 metabolic gene polymorphisms and a correlation analysis with the investigated genetic endpoints for FA-induced genotoxicity was performed. The results indicate that there are no biologically relevant differences between the three study groups with regard to the various indicators of cellular sensitivity toward FA-induced genotoxic effects and the expression of FDH. The induced genotoxic effects were not associated with polymorphisms in GSTM1 and GSTT1. None of the study groups showed particular mutagen sensitivity toward FA-induced genotoxicity. These results suggest that a low scaling factor to address possible human inter-individual differences in FA-induced genotoxicity could be reasonable.
authors.affiliation: Institut für Humangenetik, Universität Ulm, 89069 Ulm, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Zeller
authors.forename: Josef
authors.initials: J
authors.lastname: Högel
authors.forename: Regina
authors.initials: R
authors.lastname: Linsenmeyer
authors.forename: Christopher
authors.initials: C
authors.lastname: Teller
authors.forename: Günter
authors.initials: G
authors.lastname: Speit
mesh_terms: D000328:Adult; D000367:Age Factors; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003432:Cross-Linking Reagents / Q000494:pharmacology* / Q000633:toxicity; D018736:DNA Adducts / Q000737:chemistry*; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology* / Q000633:toxicity; D056726:Genetic Association Studies; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000494:pharmacology* / Q000633:toxicity; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects / Q000097:blood; D043922:Toxicogenetics / Q000379:methods; D055815:Young Adult
chemical_list: D000445:Aldehyde Oxidoreductases; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D005557:Formaldehyde; D005982:Glutathione Transferase; D009153:Mutagens; D012333:RNA, Messenger; C020145:formaldehyde dehydrogenase (glutathione); C413545:glutathione S-transferase T1