Genotoxicity of formaldehyde and an evaluation of its effects on the DNA repair process in human diploid fibroblasts.
Formaldehyde treatment of human fibroblasts gave rise to DNA damage detected by a nick translation assay. This damage was not repaired by typical 'long-patch'-type excision repair as evidenced by the failure of DNA repair inhibitor post-treatment to elevate the amount of DNA strand breakage. In addition, the effects of formaldehyde on DNA repair were examined in light of a recent report suggesting that formaldehyde inhibited the repair of X-ray-induced strand breaks and UV- and benzo [a]pyrene diol epoxide-induced unscheduled DNA synthesis in human bronchial cells. We report that formaldehyde (1) was ineffective at inhibiting the sealing of X-ray- or bleomycin-induced DNA strand breaks, (2) did not inhibit the removal of pyrimidine dimers from cellular DNA at short treatment times, and (3) that the previously observed inhibition of unscheduled DNA synthesis was most likely due to the inhibition of uptake of labeled precursor into formaldehyde-treated cells. Thus, our findings are not consistent with the notion that formaldehyde inhibits the repair process in human fibroblasts. Finally, formaldehyde was shown to elevate the level of misincorporation of bases into synthetic polynucleotides catalyzed by E. coli DNA polymerase I, indicating that the mutagenicity of formaldehyde may be due to covalent alteration of DNA bases.
R D
RD
Snyder
B
B
Van Houten
D001761:Bleomycin / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism* / Q000528:radiation effects; D004256:DNA Polymerase I / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D004171:Diploidy; D004926:Escherichia coli / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D009154:Mutation / Q000187:drug effects*; D011740:Pyrimidine Dimers / Q000378:metabolism; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D003561:Cytarabine; D001761:Bleomycin; D005557:Formaldehyde; D004247:DNA; D004256:DNA Polymerase I; D006918:Hydroxyurea