Induction of rat kidney ornithine decarboxylase by nicotinamide without a concomitant increase in DNA synthesis.

Four hours after an i.p. injection of 500 mg/kg nicotinamide, there was a decrease in kidney ODC activity, followed by a substantial increase by 24 h. Exposing rats to 0, 0.67, 6.7 and 30 mM nicotinamide in their drinking water for 7 and 28 days also resulted in a statistically significant increase in kidney ODC activity, but the rates of DNA synthesis were unaffected, as measured by incorporation of [3H]thymidine into DNA and % labeled proximal tubule nuclei; the total amount of DNA/kidney was also unaffected. The results of this investigation demonstrate that nicotinamide, a known renal tumor promoter, was able to induce a significant increase in ODC activity in the rat kidney without a concomitant increase in DNA synthesis, suggesting that early stimulation of ODC is associated with tumor promotion even in the absence of effects on DNA replication.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology