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

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Abstract
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 (6-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 procarcinogenic O6-methylguanine lesion.

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