In human cells, DNA double-strand breaks (DSBs) are repaired primarily by the 
DNA end-joining (EJ) process and thus, abnormal DNA EJ activities lead to an 
accumulation of mutations and/or aneuploidy, resulting in genetic instability of 
cells. Since genetic instability is the hallmark of cancer cells, we studied the 
DNA EJ activities of normal, non-malignant immortalized and malignant human 
epithelial cells to investigate the association between DNA EJ and 
carcinogenesis. We found a significant diminution of precise (error-free) DNA EJ 
activities in non-malignant immortalized human oral keratinocytes (HOK-16B) and 
human head and neck squamous cell carcinoma (HNSCC) cells compared to that in 
normal human oral keratinocytes (NHOK). Moreover, abnormal DNA EJ activities 
were detected exclusively in HOK-16B and HNSCC cells due to 
microhomology-mediated and non-microhomology-mediated end-joining activities in 
these cells. These data indicated that aberrant DNA EJ activity may be partly 
responsible for genetic instability and oncogenic transformation.