Effects of nitrosamines on the mitochondrial membrane

In order to clarify the biological toxities of nitrosamines, the effects of nitrosamines on the biological membrane, especially on the energy transfer reaction and on the K(+) compartmentation of mitochondria were examined. The results obtained were as follows; 1) DPNA and DBNA uncoupled the oxidative phosphorylation of rat liver mitochondria at the low concentration (about 0.2 mM solution). 2) Uncoupling activities of DPNA and DBNA to the mitochondrial oxidative phosphorylation were increased in accordance with the increase in concentration and showed a remarkable increase within the concentration range from 0.1 mM to 0.2 mM solution. 3) The release of K(+) from mitochondria was induced by treatment with DPNA or DBNA, especially was accelerated by DPNA. However, it could not be induced by treatment of 1mM DMNA or DENA. 4) The order of K(+) -release intensity induced by nitrosamines was corresponding to that of uncoupling activities of nitrosamines. 5) In conclusion, it was recognized that the functions of mitochondrial membrane were damaged by nitrosamines and their injurious effects were influenced by their chemical structures in the order of DPNA, DBNA, DENA and DMNA. This suggests that nitrosamines may have injurious effects on the function of the biological membrane, as well as their already recognized effects of carcinogenecity or liver injury (liver cirrhosis).