Induction and repair of formaldehyde-induced DNA-protein crosslinks in repair-deficient human cell lines

We have previously shown that the alkaline Comet assay (single cell gel ele ctrophoresis) in a modified version is a sensitive test for the detection o f formaldehyde-induced DNA-protein crosslinks (DPC). Our results also indic ated that formaldehyde-induced DPC are related to the formation of chromoso mal effects such as micronuclei and sister chromatid exchanges. To better u nderstand the genetic consequences of formaldehyde-induced DPC we have now investigated the induction and removal of DPC in relationship to the format ion of micronuclei in normal and repair-deficient human cell lines, We did not find significant differences between normal cells, a xeroderma pigmento sum (XP) cell line and a Fanconi anaemia (FA) cell line with respect to the induction and removal of DPC, However, the induction of micronuclei was en hanced in both repair-deficient cell lines, particularly in XP cells, under the same treatment conditions. Comparative investigations with the DNA-DNA crosslinker mitomycin C (MMC) revealed a delayed removal of crosslinks and enhanced induction of micronuclei in both repair-deficient cell lines. FA cells were found to be particularly hypersensitive to micronucleus inductio n by MMC, In contrast to the results with formaldehyde, induction of micron uclei by MMC occurred at much lower concentrations than the effects in the Comet assay. Our results suggest that more than one repair pathway can be i nvolved in the repair of crosslinks and that disturbed excision repair has more severe consequences with regard to the formation of chromosomal aberra tions after formaldehyde treatment than has disturbed crosslink repair.