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Cycle-dependent Removal of Certain Methylated Bases from DNA of 10T1/2 Cells Treated with N-Methyl-N'-nitro-N-nitrosoguanidine¹

Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514

The loss of N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced adducts from DNA was quantitated during the G₁ and S phases of synchronously proliferating mouse 10T1/2 cells exposed to MNNG (2 µg/ml) when they were in either confluence-induced arrest of proliferation or at the G₁-S border. When treated at either time, N-7-methylguanine and O⁶-methylguanine were not excised from the template DNA during the subsequent S phase. However, both lesions were efficiently removed during the G₁ phase immediately following exposure to MNNG, as well as during the second G₁ phase after an S phase during which no loss occurred. In contrast, N-3-methyl-adenine was lost rapidly during both the G₁ and S phases following MNNG treatment. N-7-Methylguanine and O⁶-methylguanine were removed from logarithmically growing cell populations more slowly than from cells passing synchronously through the G₁ phase. However, when the observed rate of loss in logarithmic cultures was corrected for the fraction of the logarithmic population located in the S phase, the rates of loss of the two methylated bases were the same as those observed in the G₁ phase in synchronous cultures.

¹ This study was supported by NIH Grants CA 24144, CA 20658, and ES 07017.

² To whom requests for reprints should be addressed.

³ Recipient of a Research Career Development Award (CA 00431).

Received 8/25/80. Accepted 12/29/80.

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