Comparative pulmonary tumorigenesis in DBA/2J and C57Bl/6J mice by administration of 3-methylcholanthrene and dimethylnitrosamine singly and combined.

C57Bl/6J mice, which are inducible for both hepatic and pulmonary aryl hydrocarbon hydroxylase (AHH), and DBA/2J mice, which are noninducible for hepatic AHH but moderately inducible for pulmonary AHH, received dimethylnitrosamine (DMN) i. p., or methylcholanthrene (MCA) orally, or a combination of both agents, for 10 weeks; the animals were observed for an additional 26 weeks. The dosing schedule and total dose of DMN or MCA or DMN + MCA received were identical to those used by other investigators in their syncarcinogenesis bioassay study in Swiss mice. The lung lesions induced in the present experiments were alveologenic tumors and adenomatosis. Alveologenic tumors were induced in a much larger number of DBA/2J mice than in C57Bl/6J mice (87.9% versus 14.0%). If, however, the sum of alveologenic tumors and adenomatous nodules is considered and is expressed per lung lesion bearing mouse, then these ratios are for the control, MCA, DMN and MCA + DMN groups: 2.7, 1.5, 3.5, and 5.4 in the DBA/2J mice and 1.0, 1.3, 2.7, and 3.6 in the C57Bl/6J mice, respectively. This suggests a relatively greater susceptibility of the C57Bl/6J strain if the ratios are compared to the respective control values. This greater susceptibility of the C57Bl/6J is best seen by comparing the percent increase of the ratio for the MCA + DMN groups; the net increase is 100% for DBA/2J and 260% for C57Bl/6J. In the DBA/2J strain more extrapulmonary tumors (hemangioendotheliomas, liver and kidney tumors) were induced than in the C57Bl/6J strain by DMN or MCA + DMN, but not by MCA alone.