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.
D000478:Alkylation; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004260:DNA Repair; D005333:Fetus; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D012867:Skin / Q000378:metabolism*
D006147:Guanine; C008449:O-(6)-methylguanine