Dose-response studies with concurrent administration of piperazine and sodium nitrite to strain A mice.

Male strain A mice were given 0.69-18.75 g piperazine/kg Food and 0.05-2.0 g sodium nitrite (NaN02)/liter drinking water For 20-25 weeks, and were killed 10-13 weeks later. The yield of lung adenomas was significantly greater than in untreated controls when as liHle as 0.69 9 piperazine/kg plus 1.0 9 NaNOdliter, or 6.25 9 piperazine/kg plus 0.25 9 NaN02/liter, were given. A maximum of 30.7 adenomas/mouse more than the controls was observed with 6.25 9 piperazine/kg plus 2.0 9 NaN02/liter. Mononitrosopiperazine (MNP) at 34.5 mg/liter drinking water induced 3.8 adenomas/mouse more than the controls. Negative results were obtained with NaN02 alone, piperazine alone, 12.3 9 sodium nitrate (NaNOa)/liter alone, or 12.3 9 NaNOa/liter plus 18.75 9 piperazine/kg. The laHer result indicated that nitrate was not reduced to nitrite under conditions suitable For reaction with the piperazine. When the piperazine concentration was raised From 0.69-18.75 g/kg Food in 3 threefold increments at a constant level of nitrite, the adenoma yield was increased between successive doses by ratios of 1.4 to 2.5. A ratio of 3.0 was predicted by application of the kinetic equation for MNP formation (adenoma yield was assumed to be proportional to MNP production). When the nitrite concentration was raised from 0.25-2.0 g/Iiter water in 3 twofold increments at a constant level of piperazine, the adenoma yield was increased by ratios of 3.7 to 3.8, in agreement with the predicted ratio of 4.0.-J Natl Cancer Inst 49: 119-124,1972.