Synergistic effects of N-nitroso compounds in experimental long-term carcinogenesis studies.

Combination effects in chemical carcinogenesis can be described either as syncarcinogenesis action of two or more carcinogens or as modified effects of noncarcinogenic substances on the action of carcinogens. Combination experiments in which one or more carcinogenic N-nitroso compounds are administered to experimental animals together with other cancer-inducing or noncarcinogenic xenobiotics show that in animal experimental animals together with other cancer-inducing or noncarcinogenic xenobiotics show that in animal experiments independent activities, additive effects, and synergistic actions as well as inhibitions may occur. After the administration of several carcinogenic substances predominantly additive effects were observed so far. A large number of experiments demonstrate the influence of different modifying xenobiotics on the action of chemical carcinogens. It is shown that in animal experiments there are real synergistic and inhibitory effects of noncarcinogenic compounds of different chemical structure on the action of chemical carcinogens. As far as the mechanism of action can be made plausible, these are either enzyme-inducing or enzyme-inhibiting effects, competitive or noncompetitive inhibitions of substrates on the enzymes, or alterations of the rate of cell division and correspondingly of the cell-specific protein synthesis. Before establishing acceptable risk values for individual chemical carcinogens it should be taken into account that as a rule interactions are to be expected in man.