Harbach P R, Swenberg J A
Carcinogenesis. 1981;2(7):575-80. doi: 10.1093/carcin/2.7.575.
Sodium selenite (Se) decreases the incidence of colon tumors induced in rats by 1,2-dimethylhydrazine (DMH). In order to determine the basis for this inhibition, we studied the effects of Se on DMH metabolism, DNA alkylation and the rate of cell turnover of the target tissue. The effects of Se pretreatment (4 p.p.m. in the drinking water, for 2, 4 or 6 weeks) on DMH metabolism were monitored in male Sprague-Dawley rats by measuring expired 14CO2 and azo[14C]methane over a 12 h period after a.c. injection of [14C]DMH (20 mg/kg body weight). Compared to control rats, which received only [14C]DMH, Se pretreatment caused an increase in exhaled azomethane (31--69%) and a corresponding decrease in 14CO2 (4--33%) as the length of treatment increased from 2 to 6 weeks. The extent of DNA alkylation (measured as N-7 and O6-methylguanine formation) after Se pretreatment was reduced 20--27% in liver and was increased 40--43% in colon. Metabolic incorporation of [14C] from [14C]DMH into adenine and guanine (presumably via C1 pathways) was reduced 69--72% in colon DNA of Se-treated rats and [3H]thymidine incorporation was reduced 61--65%. This may have been due to decreased cell turnover. A similar response was not observed in the liver. The data suggest that Se decreases hepatic DMH metabolism, and that this may be compensated by an increase in extrahepatic metabolism and alkylation. Although colon alkylation is increased by Se pretreatment, fewer tumors result. This may be due to a decrease in DNA synthesis in this tissue.
亚硒酸钠（Se）可降低1,2 - 二甲基肼（DMH）诱导的大鼠结肠肿瘤发生率。为确定这种抑制作用的基础，我们研究了硒对DMH代谢、DNA烷基化及靶组织细胞更新率的影响。通过在腹腔注射[14C]DMH（20mg/kg体重）后12小时内测量呼出的14CO2和偶氮[14C]甲烷，监测了雄性Sprague-Dawley大鼠中硒预处理（饮用水中含4ppm，持续2、4或6周）对DMH代谢的影响。与仅接受[14C]DMH的对照大鼠相比，随着处理时间从2周增加到6周，硒预处理导致呼出的偶氮甲烷增加（31% - 69%），同时14CO2相应减少（4% - 33%）。硒预处理后，肝脏中DNA烷基化程度（以N - 7和O6 - 甲基鸟嘌呤形成来衡量）降低了20% - 27%，而结肠中则增加了40% - 43%。[14C]从[14C]DMH代谢掺入腺嘌呤和鸟嘌呤（可能通过C1途径）在硒处理大鼠的结肠DNA中减少了69% - 72%，[3H]胸腺嘧啶掺入减少了61% - 65%。这可能是由于细胞更新减少所致。在肝脏中未观察到类似反应。数据表明，硒降低了肝脏中DMH的代谢，这可能通过肝外代谢和烷基化的增加得到补偿。尽管硒预处理增加了结肠中的烷基化，但产生的肿瘤较少。这可能是由于该组织中DNA合成减少所致。
