Methylation of liver DNA guanine in hydrazine hepatotoxicity: dose-response and kinetic characteristics of O6-methylguanine and formation and persistence in rats

摘要: Fischer 344 or Sprague Dawley rats were fasted overnight and given orally 30--90 mg hydrazine/kg body wt. The presence of 7-methylguanine O6-methylguanine in liver DNA was demonstrated 5 24 h after hydrazine administration using two different analytical techniques. Methylation levels changed little with dose except for the highest (ca. LD50) at which doubled. In a time-response study, 90 killed 0.25 to 96 later. Both detected quantitatively from as early 15 min administration. After maximum methylguanines had formed, removed rate approximately 50% 47 h; half-life 13 hr. Three four, but not one two, daily administrations 3 also produced detectable rat DNA. Neither comparable amounts control animals. study confirms observation that results formation methylated guanines