Repair of O6-methylguanine in human fetal brain and skin cells in culture.

The repair of O6-methylguanine was measured in cell cultures derived from human fetal brain and skin. Cells derived from nine different fetal specimens were treated in culture with N-methyl-N-nitrosourea (MNU). The brain cell cultures used were a mixture of glial and neuronal cell types, while the skin cell cultures were predominantly fibroblasts. The amount of O6-methylguanine initially induced and remaining in cellular DNA was quantitated as a function of time (0-4 h) by h.p.l.c. analysis of the acid hydrolyzates of in vitro alkylated cellular DNA. Very little (less than 10%) of the 7-methylguanine was lost from the DNA of both cell cultures 4 h post-treatment. Approximately 50% of the O6-methylguanine induced in cellular DNA by MNU was lost within 0.7 h in both the human fetal brain and skin cells in culture. Within 4 h, 80% of this methylated guanine was lost. The kinetics for the removal of O6-methylguanine in the brain and skin cells appeared biphasic. A rapid initial phase was followed by a gradual slower phase of repair. These studies indicate that cells derived from human fetal brain and skin exhibit the same degree of proficiency for the repair of the potential pro-carcinogenic O6-methylguanine lesion.