Sequential electron microscopical study of experimental mouse skin carcinogenesis.

Abstract

AbstractElectron microscopical study of experimentally induced skin tumours was undertaken. The investigation was designed to determine the sequence of morphological changes between first painting with a carcinogen (methylcholanthrene) and the development of invasive neoplasms. It was found that changes occurred in both the epidermis and the dermis but that the most profound disturbances affected the region of the dermoepidermal junction.The epidermal changes corresponded to those described by previous investigators. Changes in dermal organization appeared by the end of the second week. These consisted mainly of a decrease in the size of collagen fibres and a relative increase in connective tissue ground substance. There was also an increase in the dermal cell population, many of the new arrivals being mast cells. Examination of the dermo‐epidermal junction revealed that the basement membrane was thickened and in several places had separated slightly from the basal epidermal cells.After five to six weeks' painting, small gaps appeared in the basement membrane. These were accompanied by the accumulation of fragmented material, similar in consistency to the basement membrane, in the superficial dermis. Where this material lay close to mast cells it appeared to coalesce to form reduplicated basement membranes.By the time papillomas appeared, reduplication of the basement membrane had ceased and basement membrane material was decreasing. The dermal aspects of the basal cells pushed out cytoplasmic projections into the connective tissue. These projections constricted and separated from the cell to produce free‐lying vesicles in the superficial dermis. Later the vesicles ruptured and the release of their contents was associated with destruction of small areas of surrounding connective tissue. These appearances suggested enzymatic destruction of dermis by epidermis.The dermo‐epidermal junction of carcinomas showed similar but more pronounced changes of which complete absence of basement membrane, vesicular activity of basal cells and gross disorganization of surrounding connective tissue were the most characteristic features.Preliminary studies indicated that similar changes occur in spontaneous and experimentally induced breast tumours.