Localization of stratum of maxium mitotic frequency in epidermal methylcholanthrene carcinogenesis in mice.

The purpose of the major cancer research project of Barnard Hospital is to measure the properties of epidermis during epidermal carcinogenesis induced by methylcholanthrene, to integrate the findings and thus to construct a comprehensive account of what .happens (6). Mitotic frequency is one of these properties and has been investigated by Cooper and Relier (5) and by Reller and Cooper (12). They have observed that 18 hours after the initial application of methylcholanthrene there is a distinct increase in mitotic frequency over that exhibited by normal epidermis, that this increase grows in magnitude to 16 days, that it is maintained fairly constant to 51 days, when it decreases only to increase again about the time that cancers make their appearance in the series. Since these observations were based on counts of mitoses and of nondividing nuclei made on preparations of whole epidermis mounted with proximal, that is dermal, surface uppermost which were viewed vertically, it was not possible to identify the epidermal strata in which the mitoses occurred. The counts were therefore total for whole epidermis, not differential for its several strata. Differential counts of mitotic frequency can be made only on stained sections of epidermis which are vertical to the surface and which cut across the strata at right angles. But the epidermis of the area chosen for treatment with carcinogen is normally so thin (2 to 3 strata) that in it the strata, easily identifiable in the early hyperplastic stages of carcinogenesis, are not represented. Consequently, it was necessary to make differential counts of mitotic frequency on much thicker epidermis of mice, which normally is stratified, in order to secure data on the basis of which to interpret differential counts of epidermis in our carcinogenic series. Cowdry and Thompson (9) selected for this purpose epidermis of the hind foot pads of mice of the same New Buffalo strain used in the major project. They produced a summation of mitoses by injecting the mice with