Comparison of virus reactivation, DNA base damage, and cell cycle effects in autologous human melanoma cells resistant to methylating agents.

A human melanoma cell line (MM253c1-3D) having an induced stable resistance to the methylating agents 5-(3'-methyl-1-triazeno)imidazole-4-carboxamide, methylnitrosourea, and N-methyl-N'-nitro-N-nitrosoguanidine gave more efficient replication of 5-(3'-methyl-1-triazeno)imidazole-4-carboxamide-treated adenovirus 5 than did the methylation-sensitive parent line (MM253c1). Analysis of DNA hydrolysates from melanoma cells treated with [3H]methylnitrosourea for 1.6 hr showed similar initial levels of 7-methylguanine and 3-methyladenine in both cell lines and substantial excision of the latter lesion after 19 hr. O6-Methylguanine in the DNA of MM253c1 cells also decreased during this period, but in MM253c1-3D cells the initial yield of this lesion was too low for subsequent decrease to be detected. 5-(3'-Methyl-1-triazeno)imidazole-4-carboxamide induced a significant arrest of MM253c1 cells in the G2 phase of the cell cycle. These results show that MM253c1 is a variant of the Mer- phenotype, the resistance of MM253c1-3D cells being attributed to reversion to Mer+ and expressed as very rapid repair of O6-methylguanine lesions.