Methylation of DNA in various organs of c57b1 mice by a carcinogenic dose of N-methyl-N-nitrosourea and stability of some methylation products up to 18 hours

Female 6–8-week-old C57B1 mice were injected i.p. with N-methyl-N-nitrosourea (MNUA) (¹⁴C or ³H-methyl-labelled) in saline (80 mg/kg) and DNA was isolated from bone marrow, small bowel, kidneys, liver, lungs, spleen and thymus at various times thereafter up to 18 h. Methylation of DNA was found in all organs examined, and by analyses using column or paper chromatography of DNA hydrolysates, the extent of methylation of DNA purines was determined.Methylated guanine residues (at N-3, N-7 and O-6 positions) were stable in DNA up to 18 h, but methylated adenines (at N-3 or N-7) were removed from DNA of all organs examined; the overall half-life of methyladenines was about 3 h, but removal appeared to occur in a biphasic manner, with a proportion of methyladenine remaining relatively stable. This relative stability was somewhat more marked in bone marrow than in other organs.