Patterns of Damage and Repair of Liver DNA Induced by Carcinogenic Methylating Agents in Vivo¹

Single-strand breaks induced by methylating agents in liver DNA and their rejoining were studied in vivo by the use of alkaline sucrose gradients. DNA breaks were induced by the i.p. injection of single doses of dimethylnitrosamine (DMN), methylazoxymethanol acetate (MAM), N-methyl-N-nitrosourea (MNU), and N-methyl-N-nitrosourethan. The degree of damage was dependent on the dose of the substance given. DMN and MAM are comparably efficient in inducing marked single-strand breaks of liver DNA in small doses. MNU, although noncarcinogenic for liver, causes single-strand breaks of liver DNA, while N-methyl-N-nitrosourethan causes less damage even at toxic doses. The repair of the damage to DNA induced by MNU was complete in the first week while that induced by DMN and MAM was still not complete within 14 days after administration of the compond. Thus, the repair of the damage induced by hepatocarcinogens (DMN and MAM) seemed to be slower than that with the methylating agents not carcinogenic for the liver (MNU and methyl methanesulfonate).