Tiazofurin-induced selective depression of NAD content in hepatoma 3924A.

The NAD content in hepatoma 3924A was approximately 40% of that in the liver of ACI/N rats bearing this hepatoma. Treatment of tumor-bearing rats with tiazofurin decreased NAD pools in the hepatoma, but no change was apparent in the liver. In a dose-response study, injection of varying amounts of the drug decreased NAD pools in the hepatoma in a dose-dependent fashion. In time-sequence studies, a single drug dose (200 mg/kg) depressed NAD pools in the hepatoma from 2 to 24 h after injection to approximately 50% of control at the lowest point before returning to control range at 48 h. The tiazofurin-induced depletion of NAD pools in the hepatoma to approximately 20% of that of normal liver might play a role in the anti-cancer action and toxicity of this drug.