STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY : III. SPONTANEOUS TUMORS OF THE LUNG IN MICE.

1. The occurrence of tumors in the lung in mice is dependent to a certain extent upon the age of the individual. No tumors were found in the lungs of mice less than 8 months old. They occurred with greatest frequency in mice of about 24 months or older. Mice may live to be more than 3 years old without developing growths in the lung. These facts show that the development of tumors of the lung, if hereditary, is a variable character. An individual, genetically a tumor mouse, may live to a great age without showing a tumor if the requisite environmental stimulus (external or internal) is lacking. Sex if effective at all has a comparatively slight influence upon the incidence of lung tumors. 2. Two strains of mice were studied which exhibit differences in their rates of incidence of lung tumors that are large enough to be significant. The conflict in the evidence from different laboratories as to whether or not tumors of the lung are the commonest type found in mice, is probably to be explained on the basis of a differing hereditary tendency to such growths in differing stocks. 3. Data from a number of sources indicate that offspring from parents free from lung tumors have a lower rate of lung tumor incidence than offspring from parents one of which had a tumor. If both parents had lung tumors the rate of tumor incidence among their offspring is increased still further. 4. In crosses between mice from strains which have high and low rates of incidence of lung tumor, tumors appeared in about half of the individuals of the first generation and in about one-quarter of the second generation. If the character responsible for the development of the growths is recessive it should not be found in the first filial generation unless both parents are carrying it. There is no proof that the female parents did not carry it but since they were taken from a strain in which the incidence of the growths was but 6.7 per cent the chances seem good that they were free from it. This suggests that the character determining the incidence of pulmonary tumors may be a dominant one. A dominant character is not expected to appear among the offspring from parents neither of which has shown the character. The numerous instances which have been tabulated in this paper of mice with lung tumors among the offspring of parents free from lung tumors, must be explained on the assumption that tumor susceptibility is not only dominant but variable and that some of the parents which did not actually develop tumors were genetically tumor mice and had the capacity for developing tumors although it was not brought out. As we have already concluded on the basis of the relationship between age and tumor incidence that susceptibility to the development of lung tumors is a variable character our explanation of the occurrence of tumor mice derived from tumor-free parents is justifiable. The existence of strains of mice with rates of incidence of lung tumors that differ as widely as do the two that we have studied, the relatively high incidence of pulmonary growths among mice of tumor parentage as compared with mice from non-tumor parents, and the fact that females from a strain in which pulmonary tumors are rare when crossed with individuals from a strain in which they are frequent give a fairly high rate of incidence of the growths among the first and second filial generations,-all these facts indicate that susceptibility to the development of tumors in the lung is an inherited character.