THE INITIATING AND PROMOTING ELEMENTS IN TUMOR PRODUCTION : AN ANALYSIS OF THE EFFECTS OF TAR, BENZPYRENE, AND METHYLCHOLANTHRENE ON RABBIT SKIN.

Benzpyrene brings about neoplastic changes in rabbit epidermis much sooner than has been supposed. The long interval that elapses before visible growths appear is due in the main to the relatively slight power of the carcinogen to encourage multiplication of the cells it renders neoplastic. Yet some slight power of this sort it has. Methylcholanthrene has somewhat more but not nearly so much as tar. It may initiate neoplastic changes within less than 17 days, as compared with less than 10 days for tar, but tumors due to it do not ordinarily appear until months after those called forth by tarring. All three agents give rise to growths of essentially the same kinds, but most of those due to benzpyrene and methlycholanthrene remain for a long while small, dry, and indolent whereas many of the tar tumors are fleshy, vigorous, and rapidly enlarging,-differences wholly consequent on differences in the ability to promote growth. Such ability is an important element in the effectiveness of carcinogens. Tar and the polycyclic hydrocarbons cause many more cells to become tumor cells than give rise to visible growths. Benzpyrene is as effective in initiating neoplastic changes when dissolved in mineral oil as when in benzene, yet no tumors result from it until months after the benzene solution has given rise to them, the reason being that when in oil it is almost devoid of influence to encourage cell proliferation. Benzene itself has a very slight influence of the sort. Solvents may determine not only whether carcinogens initiate neoplastic change but may condition to a crucial degree the influence of these agents to encourage tumor formation. Rabbit epidermis is much more responsive to carcinogenic influences than that of the mouse, as measured in terms of time taken to elicit benign neoplasms. Even benzene will call forth these growths from rabbit skin. In appraising the relative responsiveness to carcinogens of various animal species it is essential to reckon in terms of cells of identical type.