Radiosensitizing effects of nicotinamide on a C3H mouse mammary adenocarcinoma. A study on per os drug administration.

Abstract

Nicotinamide is an inhibitor of adenosine diphosphate ribosyl transferase (ADPRT) which is involved in the mechanism of DNA repair after high doses of ionizing radiation. C3H mice with transplanted mammary adenocarcinomas were treated with low doses of nicotinamide, 10 mg/kg, 5 days a week, and in combination with ionizing radiation, 30 Gy, using different drug dose schedules. Mice given nicotinamide in combination with irradiation took a longer time to reach a tumor volume of 1,000 mm3 and a higher complete response rate (i.e. defined as total disappearance of the tumor for at least 7 days) than those given radiation alone. This was true whether nicotinamide was given daily from one week before tumor transplantation until the animal was killed or from transplantation day until day of irradiation. In addition, nicotinamide given per os at a dose between the recommended maximum daily allowance for human subjects (20 mg/70 kg), and the therapeutic allowance (1 g-12 g daily) 5 days a week for 9 weeks, showed a radiosensitizing effect without any histologically detectable damage to the normal tissues of the mouse, including bone marrow, intestine and the liver.