The human lung cell line A549 does not develop adaptive protection against the DNA-damaging action of formaldehyde.
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 microM) did not lead to significant differences in the induction of DPX in comparison with a single treatment. Pretreatment with higher FA-concentrations (200 microM 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 microM) 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 microM) 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.
Speit
Günter
G
Universität Ulm, Institut für Humangenetik, Ulm, Germany. guenter.speit@uni-ulm.de
Neuss
Simone
S
Schmid
Oliver
O
D000222:Adaptation, Physiological / Q000235:genetics*; D000426:Alcohol Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D020552:Comet Assay; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008658:Inactivation, Metabolic; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050697:Retinal Dehydrogenase; D013997:Time Factors
D005557:Formaldehyde; D004247:DNA; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases; D000080924:Aldehyde Dehydrogenase 1 Family; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase