Cooper H K, Buecheler J, Kleihues P
Cancer Res. 1978 Sep;38(9):3063-5.
The formation and persistence of methylated purines was determined in mice that received a single s.c. injection of 1,2-[14C]dimethylhydrazine (15 mg/kg) and were allowed to survive for 12 or 60 hr. In mice with a low susceptibility to dimethylhydrazine-induced colon carcinogenesis (C57BL/Ha), concentrations of 7-methylguanine and O6-methylguanine in DNA of colon, ileum, and kidney were 40 to 60% less than in mice with a high incidence of colonic tumors (ICR/Ha). In hepatic DNA the extent of methylation was higher in C57BL/Ha than in ICR/Ha mice. The rate of loss of methylated purines from colon DNA was similar in both strains. In all organs investigated the metabolic incorporation of 14C into normal DNA bases was lower in C57BL/Ha than in ICR/Ha mice. It is concluded that the low carcinogenic response of C57BL/Ha mice is due to the smaller extent of initial alkylation of colon DNA, which probably reflects differences in the enzymic metabolism of the parent carcinogen.
对接受单次皮下注射1,2-[¹⁴C]二甲基肼（15毫克/千克）并存活12或60小时的小鼠，测定甲基化嘌呤的形成和持久性。在对二甲基肼诱导的结肠癌发生敏感性较低的小鼠（C57BL/Ha）中，结肠、回肠和肾脏DNA中7-甲基鸟嘌呤和O⁶-甲基鸟嘌呤的浓度比结肠肿瘤发生率高的小鼠（ICR/Ha）低40%至60%。在肝脏DNA中，C57BL/Ha小鼠的甲基化程度高于ICR/Ha小鼠。两种品系中结肠DNA甲基化嘌呤的丢失率相似。在所有研究的器官中，C57BL/Ha小鼠中¹⁴C代谢掺入正常DNA碱基的量低于ICR/Ha小鼠。结论是，C57BL/Ha小鼠致癌反应低是由于结肠DNA初始烷基化程度较小，这可能反映了母体致癌物酶代谢的差异。
