In order to study the role of DNA damage processing in the development of 
cutaneous squamous cell carcinoma (SCC), we assessed the ability of six 
keratinocyte cell lines from a multistage-tumor progression model to repair 
three types of DNA damage: pyrimidine dimers, oxidative DNA lesions and DNA 
double strand breaks (DSB). The model comprised the spontaneously immortalized, 
non-tumorigenic human keratinocyte cell line HaCaT, four different c-Ha-ras 
transfectants of HaCaT (non-, benign- and two malignant-tumorigenic) and a 
SCC-derived cell line. Host cell reactivation assays with UVB-treated plasmid 
vectors pRSVcat showed no significantly altered repair of UVB-induced pyrimidine 
dimers in the tumorigenic cell lines, compared with the non-tumorigenic lines. 
Using the singlet oxygen-treated plasmids pRSVcat the Ha-ras-HaCaT-clones and 
the SCC-cells, exerted a DNA repair efficiency that was not significantly 
different from HaCaT cells. In order to assess the ability of the cells to 
ligate free DNA ends (repair of DSB), we used a plasmid shuttle vector assay 
with linearized plasmid pZ189. We found a significant increase of DNA end 
joining ability in the non-tumorigenic, the benign and in one of the malignant 
HaCaT-clones II-4. The malignant HaCaT-clone II-3, however, exerted a 
significantly lower rate of rejoining the linearized plasmid. This cell line 
also showed a highly and significantly elevated rate of micronuclei, which 
reflects a pronounced chromosomal instability. The SCC-cells exhibited a more 
efficient repair of DNA DSB than the HaCaT cells. We conclude that in the 
examined model, progression of human keratinocytes from the non-tumorigenic to 
the highly tumorigenic phenotype, is not accompanied by a decrease in the cell's 
capacity to repair UVB- and singlet oxygen-induced DNA lesions. However, an 
acquired deficiency in repairing DNA double strand breaks can be one mechanism 
promoting progression towards malignancy, possibly through impairing chromosomal 
stability.