Experiments were carried out to learn whether the widely differing liabilities to induced epidermal tumors of individual mice and rabbits are due to a previous localization out of the blood of an agent capable of undergoing change when the skin is exposed to carcinogenic influences, and of producing tumors in consequence. On the assumption that such an agent would localize in increased quantity where cutaneous inflammation exists, like various inert substances of large molecule and the epidermotrophic viruses when circulating, skin areas on adult and new-born animals were for some weeks kept inflamed, and months later, when the areas appeared normal, methylcholanthrene was applied to them and to control areas on the same or other individuals. No differences were observable in tumor incidence.
These results led to attempts to test whether embryo epidermis is capable of undergoing neoplastic change, and the work of Paper I was done which showed that epidermal tumors arise with great rapidity and regularity from embryo skin transplanted to adults of homologous strain (C strain) together with methylcholanthrene. Webster-Swiss mice proved unsuited to experiments of the sort owing to heterogeneity of the breed, the transplanted embryo skin dying in most instances before the methylcholanthrene introduced with it could have been carcinogenic. The skin of C3H embryos also did badly, as if from incompatibility in some instances but mostly because its epidermal cells proliferated less vigorously than those of C embryos and did not tolerate methylcholanthrene nearly so well. Despite these difficulties, epidermal tumors were occasionally induced, as also in the transplanted skin of Webster-Swiss embryos, and the growths appeared quite soon, all things considered.
The effect of methylcholanthrene on the skin of sucklings, their mothers, and young adult mice of the C strain was studied in order to find out whether the rapid rate of neoplastic change in the transplanted epidermis of embryos is indicative of some liability connected with its period of development. The skin of new-born animals proved very refractory to the carcinogen, hair coming in at the same rate as on control litters and no perceptible inflammation occurring for about 2 weeks, although within this period the mothers of the treated animals and the young adults became hairless where the methylcholanthrene had been put and their skin was much inflamed. Later on, as the applications were kept up, similar changes took place in the sucklings, but none of these developed tumors during some 6 weeks of observation whereas growths appeared within 3 weeks on more than half of the mother mice and on some of the young adults. The failure to produce tumors in the sucklings seems to have been due to cutaneous conditions preventing the necessary exposure of the deeper epidermal cells to methylcholanthrene. In any projected correlation of age differences with the response of cells to carcinogens allowance must be made for such factors. The present findings give no ground for the supposition that embryo skin has any special liability to neoplastic change.
The results of transferring the tumors derived from embryo epidermis to new hosts have made plain that the neoplastic state not infrequently entails disabilities which are crucial, the tumor cells failing to succeed unless aided. This holds true of some carcinomas as well as of papillomas.
By transplanting pieces of the organs of C embryos together with methylcholanthrene tumors of many sorts besides the epidermal have been obtained. As yet only those of the stomach have been worked with extensively. They can be elicited as quickly and regularly as those of the epidermis and can be as easily transplanted.
The findings as a whole render it impossible to suppose that the neoplastic potentialities possessed by transplanted embryo tissues are due to the lodgement in them of tumor-producing viruses as specialized in their effects as those now known, or of precursor agents conferring neoplastic liabilities specialized to the same degree. Some other possibilities are mentioned.
The rarity of neoplasms at birth is due to the circumstances of intrauterine life and to its brevity, not to any lack of capacity of the cells of the embryo to undergo neoplastic change.