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The human lung cell line A549 does not develop adaptive protection against the DNA‐damaging action of formaldehyde
Author(s) -
Speit Günter,
Neuss Simone,
Schmid Oliver
Publication year - 2010
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20524
Subject(s) - a549 cell , aldehyde dehydrogenase , chemistry , cell culture , aldh2 , microbiology and biotechnology , dna damage , formaldehyde dehydrogenase , glutathione , alcohol dehydrogenase , cytosol , dna repair , comet assay , enzyme , biochemistry , dna , cell , biology , genetics
The alkaline comet assay was used to further characterize the induction of DNA‐protein crosslinks (DPX) by formaldehyde (FA) and their removal in the human lung cell line A549. DPX were indirectly measured as the reduction of gamma ray‐induced DNA migration. Repeated treatments of A549 cells with low FA concentrations (up to 100 μM) did not lead to significant differences in the induction of DPX in comparison with a single treatment. Pretreatment with higher FA‐concentrations (200 μM and above) enhanced the crosslinking effect. There was no indication for an adaptive protection against the induction of DPX by FA. These findings are in agreement with RT‐PCR measurements of the expression of genes that encode the main enzymes involved in FA detoxification. A549 cells exposed to FA (50–300 μM) for 1, 4, or 24 hr did not reveal altered expression of the GSH‐dependent formaldehyde dehydrogenase ( FDH , which is identical to alcohol dehydrogenase 3; ADH3 ), the cytosolic aldehyde dehydrogenase 1 ( ALDH1A1 ) and the mitochondrial ALDH2 . Pretreatment of A549 cells with a low FA concentration (50 μM) also did not enhance the removal of DPX induced by higher FA concentrations. Taken together, these results suggest that A549 cells do not develop adaptive protection against the genotoxic action of FA. Neither metabolic inactivation of FA nor the repair of FA‐induced DPX seems to be enhanced in cells pretreated with FA. Environ. Mol. Mutagen., 2010. © 2009 Wiley‐Liss, Inc.