Mazin A L
Mol Biol (Mosk). 1993 Jan-Feb;27(1):160-73.
The 5-methylcytosine (5mC) content in liver DNA has been determined for rats of different age. The rate of the 5mC loss from DNA is maximal in pre- and neonatal rats, 1.28% of reduction of the 5mC content per day, then it decreases to 0.33% and becomes minimal and constant in adult rats, 0.028% per day. During pregnancy and the first 15 days of postnatal development rat genome loses 49% of all 5mC. Within the next 45 days 15% of 5mC disappears, and during maximal rat life span, about four years, 39% of the genomic 5mC may be lost. Thus, it has been found for the first time that the animal genome loses practically all 5mC residues during the life span. Analysis of the literature data shows that for embryos the rate of the 5mC loss from DNA proves to be higher than that for adult animals by 96 times for mice, 69-for rats and 28-for cows. The rate of embryonal DNA hypomethylation may be inversely proportional to the pregnancy duration of species. In adult animals the rate inversely correlates with their maximal life span and accounts for the 5mC loss from DNA of a mouse by 0.028%, of a rat by 0.024%, of a hamster by 0.007%, of a cow by 0.004% and of a human being by 0.0005% per day. During the entire ontogenesis, the genome of a mouse loses 93% of all 5mC residues, that of a rat-101% and of a cow-88%. The age-dependent loss of 5mC from DNA is also typical for cell lines aging in vitro. It is constant, as a rule, and correlates with the number of cell population doublings (PD). The removal of all 5mC from DNA corresponds to 70-130 PD for human, 40-60 PD-for hamster and 6 PD- for mouse cells. In immortal lines the level of DNA methylation is stable or grows with age. A possible mechanism of an age-related 5mC loss from DNA is discussed. DNA hypomethylation may result from 5mC deamination directly at the moment of replicative DNA methylation and subsequent reparation of the G.T mispairs which leads to accumulation of the 5mC-->T+C substitutions in the genome with each cell division. So DNA methylation may serve as an ideal mechanism for counting cell divisions in vivo and in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
已测定不同年龄大鼠肝脏DNA中的5-甲基胞嘧啶（5mC）含量。DNA中5mC的丢失率在出生前和新生大鼠中最高，每天5mC含量降低1.28%，然后降至0.33%，在成年大鼠中变得最低且恒定，每天为0.028%。在怀孕和出生后发育的前15天，大鼠基因组会丢失所有5mC的49%。在接下来的45天内，15%的5mC消失，在大鼠最长约四年的寿命期间，基因组中39%的5mC可能会丢失。因此，首次发现动物基因组在其寿命期间几乎会丢失所有5mC残基。对文献数据的分析表明，对于胚胎，DNA中5mC的丢失率经证明比成年动物高，小鼠高96倍，大鼠高69倍，奶牛高28倍。胚胎DNA低甲基化的速率可能与物种的孕期成反比。在成年动物中，该速率与它们的最长寿命呈负相关，小鼠DNA中5mC的每日丢失率为0.028%，大鼠为0.024%，仓鼠为0.007%，奶牛为0.004%，人类为0.0005%。在整个个体发育过程中，小鼠基因组会丢失所有5mC残基的93%，大鼠为101%，奶牛为88%。DNA中5mC随年龄的丢失在体外老化的细胞系中也很典型。通常是恒定的，并且与细胞群体倍增次数（PD）相关。从DNA中去除所有5mC相当于人类细胞70 - 130次PD，仓鼠细胞40 - 60次PD，小鼠细胞6次PD。在永生化细胞系中，DNA甲基化水平稳定或随年龄增长。文中讨论了DNA中与年龄相关的5mC丢失的一种可能机制。DNA低甲基化可能是由于在复制性DNA甲基化时5mC直接脱氨基，随后修复G.T错配，这导致随着每次细胞分裂基因组中5mC→T + C替代的积累。因此，DNA甲基化可能是体内和体外计算细胞分裂次数的理想机制。（摘要截取自400字）
