The inducibility of two DNA repair
proteins, the O6-methylguanine-DNA-methyltransferase (MGMT) and the
N3-methyladenine-DNA-glycosylase (ANPG), was studied by measuring the
protein activities and the transcription of the MGMT and ANPG genes in a human
hepatoma cell line (LICH cells). The two
protein activities are enhanced
after treatment with a variety of
DNA-damaging agents. They are maximum 72 hr after the inducing treatments and remain elevated for about 120 hr. This induction is abolished when the cells are grown in the presence of
protein or
RNA synthesis inhibitors. Northern blot analysis shows that the
DNA-damaging agents increase to different extents the transcription of the MGMT or ANPG genes. The
transferase activity is also increased by DNA damage in a human
glioblastoma cell line (T98G cells), but is not significantly modified in human normal fibroblasts, suggesting that this repair activity enhancement might occur preferentially in transformed cells, as we have previously shown for cells of rat origin. Therefore, these increased repair activities may play an important role in removing the lethal
N3-methyladenine residues, the promutagenic
O6-methylguanine lesions, and the potentially lethal chloroethyl adducts formed by the nitrosoureas used in
cancer chemotherapy more efficiently from the cellular
DNA.