In vivo replication of carcinogen-modified rat liver DNA: increased susceptibility of O6-methylguanine compared to N-7-methylguanine in replicated DNA to S1-nuclease

In order to characterize rat liver DNA replicated $\text{in}\text{vivo}$ on a carcinogen-damaged template, the replicated DNA was treated with S₁-nuclease and the release of (¹⁴C)-dimethyl-nitrosamine induced 0⁶-methylguanine, a lesion associated with miscoding and N-7-methylguanine, a lesion that does not miscode were monitored. The results indicated that both the methylated guanines became susceptible to S₁-nuclease upon replication. However, a greater percentage of 0⁶-methylguanine (22% of the total 0⁶-methylguanine present in the DNA) compared to N-7-methylguanine (4% of the total N-7-methylguanine present in the DNA) was rendered acid soluble by S₁-nuclease. The preferential release of 0⁶-methylguanine compared to N-7-methylguanine from replicated DNA was interpreted to indicate its occurrence in local denatured regions probably generated as a result of misbase pairing.