Combined Carcinogenic Effects of Dimethyl-nitrosamine and 3-Methylcholanthrene in the Rat

Summary

To study the influence of increased tissue N-demethylase, induced by 3-methylcholanthrene (MCA), on the carcinogenicity of di-methylnitrosamine (DMN), the effect of the simultaneous feeding of these carcinogens to rats was studied. Feeding MCA alone unexpectedly induced subcutaneous sarcomas in adult rats. The combined feeding of MCA and DMN did not increase the number of hepatic tumors known to be induced by the nitrosamine. At the low total dose level used here, DMN alone did not induce tumors in the lung; it did, however, induce lung tumors when administered with MCA. The incidence of subcutaneous sarcomas was slightly increased by the simultaneous administration of DMN. Also skin tumors arose in the group receiving the 2 carcinogens simultaneously. These phenomena have been interpreted in the framework of the alkylation hypothesis of nitrosamine carcinogenesis.