Influence of administration route and dosage schedule on tumor response to nitrosoheptamethyleneimine in rats

Nitrosoheptamethyleneimine (NHMI) was tested for carcinogenicity in Fischer-344 and Sprague-Dawley rats by intragastric administration and subcutaneous injection. Cumulative doses ranged from 5.5 to 1,200 mg/kg, and dosage schedules ranged from 40 serial administrations to one single injection. No difference in response was seen between sexes or strains of rats. Following the highest carcinogen doses by intragasritc administration, a high incidence of squamous-cell tumors occurred in the lung. The highest incidence of squamous-cell tumors occurred in the nasal cavity, trachea and esophagus. Following subcutaneous injection, tumors induced in the lungs were all alveologenic adenocarcinomas. The upper respiratory and gastrointestinal tracts were again the most commonly affected sites, with tumors similar to those of the first group. Intragastric administration was more effective in producing tumors than was subcutaneous injection, and administration of multiple small doses was more efficient than single large doses. The results demonstrated that the route and schedule of administration markedly influenced the tumor response to NHMI, both quantitatively and qualitatively.