title: Investigations on potential co-mutagenic effects of formaldehyde.
abstract: The genotoxicity and mutagenicity of formaldehyde (FA) has been well-characterized during the last years. Besides its known direct DNA-damaging and mutagenic activity in sufficiently exposed cells, FA at low concentrations might also enhance the mutagenic and carcinogenic effects of other environmental mutagens by interfering with the repair of DNA lesions induced by these mutagens. To further assess potential co-mutagenic effects of FA, we exposed A549 human lung cells to FA in combination with various mutagens and measured the induction and removal of DNA damage by the comet assay and the production of chromosomal mutations by the cytokinesis-block micronucleus assay (CBMN assay). The mutagens tested were ionizing radiation (IR), (±)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), N-nitroso-N-methylurea (methyl nitrosourea; MNU) and methyl methanesulfonate (MMS). FA (10-75μM) did not enhance the genotoxic and mutagenic activity of these mutagens under the test conditions applied. FA alone and in combination with MNU or MMS did not affect the expression (mRNA level) of the gene of the O(6)-methylguanine-DNA methyltransferase (MGMT) in A549 cells. The results of these experiments do not support the assumption that low FA concentrations might interfere with the repair of DNA damage induced by other mutagens.
authors.affiliation: Universität Ulm, Institut für Humangenetik, 89069 Ulm, Germany. Electronic address: guenter.speit@uni-ulm.de.
authors.forename: Günter
authors.initials: G
authors.lastname: Speit
authors.affiliation: Universität Ulm, Institut für Humangenetik, 89069 Ulm, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Linsenmeyer
authors.affiliation: Universität Ulm, Institut für Humangenetik, 89069 Ulm, Germany.
authors.forename: Giang
authors.initials: G
authors.lastname: Duong
authors.affiliation: Universität Ulm, Institut für Humangenetik, 89069 Ulm, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bausinger
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000009:adverse effects; D000477:Alkylating Agents / Q000009:adverse effects; D002869:Chromosome Aberrations / Q000187:drug effects*; D020552:Comet Assay; D004202:Disinfectants / Q000009:adverse effects*; D004338:Drug Combinations; D004357:Drug Synergism; D005557:Formaldehyde / Q000009:adverse effects*; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008741:Methyl Methanesulfonate / Q000009:adverse effects; D008770:Methylnitrosourea / Q000009:adverse effects; D015162:Micronucleus Tests; D009153:Mutagens / Q000009:adverse effects*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000477:Alkylating Agents; D004202:Disinfectants; D004338:Drug Combinations; D009153:Mutagens; D012333:RNA, Messenger; D005557:Formaldehyde; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D008770:Methylnitrosourea; D008741:Methyl Methanesulfonate; D019853:O(6)-Methylguanine-DNA Methyltransferase
keywords: Comet assay; DNA repair; Gene expression; Micronucleus test; O(6)-methylguanine-DNA methyltransferase