The most important stages of the mechanism of action in vivo of carcinogen diethylnitrosoamine and its effect on the synthesis of RNA,proteins, DNA,and deoxyribonucleotides

The mechanisms of nitric oxide (NO) generation from exogenous and endogenous sources, induced by the addition of the carcinogen diethylnitrosoamine (DENA) to rat organism have been studied. Within 15 h after the addition of DENA, the carcinogen itself acts as an exogenous NO donor. The products of protein degradation (the process induced by DENA) act as endogenous donors of NO. It was shown that the generation of NO from DENA leads to deep hemic and tissue hypoxia and induces the inactivation of oxygen-dependent enzymes, including ribonucleotide reductase, and the inhibition of ATP synthesis. Under these conditions, the protein synthesis and as a consequence the synthesis of deoxyribonucleotides and DNA are strongly suppressed; i.e., DENA produces the effect similar to the action of the antibiotic cycloheximide, an inhibitor of translation. The administration of cycloheximide to the animal organism also led to the appearance of a considerable amount of NO in the blood. It is assumed that NO initiates (on the administration of the carcinogen) or at least enhances (on the administration of cycloheximide) the blockage of the synthesis of the protein, deoxyribonucleotides, and DNA. In response to the disturbance of protein synthesis, the complex of enzymes is activated that accomplish the utilization of the degradation products of proteins, including the inducible form of NO synthase.