CAECINOGENESIS 123 



to the mouse skin induces almost immediately a marked epidermal hyper- 

 plasia which involves also the hair follicles — depending on their stage in the 

 hair cycle and also causes a squamous metaplasia of the sebaceous glands. The 

 dermal and vascular changes are at first very slight, though later on a mild 

 inflammatory reaction is found and also a replacement of the dense dermal 

 fibres particularly in the superficial regions by a thin-fibred, cellular connec- 

 tive tissue. With continued painting the hyperplasia shows quantitative 

 variations coinciding with the hair cycle, and leads after about two months to 

 the formation of papillomas. These are formed by epidermal proliferations as 

 well as by abortive hair follicles in which proliferation replaces the normal 

 production and differentiation of hairs. These changes occur over a wide 

 field and lead to the confluence of neighbouring hyperplastic and papilloma- 

 tous foci. After about eighty-four days, invasive tumours are found which 

 infiltrate and penetrate the panniculus carnosus. Thus in chemical carcino- 

 genesis a cellular proliferation with delayed maturation of the potential 

 dividing cells of the epidermis and the hair follicles is induced and this change 

 is followed subsequently by the acquisition of new characters of the cells 

 consisting of their assumption of morphological and fmictional anaplasia. 

 The morphological anaplasia is indicated by increased proliferative activity, 

 decreased ability for differentiation, by loss of adhesiveness of cells, loss of 

 polarity and ability to invade other structures. The functional anaplasia is 

 seen in the ability of the tumour tissue to grow at other sites in the same 

 host — i.e. in metastatic localizations — and in other hosts, i.e. the acquisition 

 of transplantability. These changes occur at irregular intervals, often as 

 separate steps but always in the descendants of the originally treated cells. 



In mice given a single dose of8,000rads from an electron beam generated at 

 0-7 MeV over a circular area of 1 cm diameter the histological changes are as 

 follows: mitotic inhibition in the epidermis and in the hair follicles is followed 

 by a hyperkeratosis and, with the absence of replacing basal cells, the kera- 

 tinized epidermal layers and the hair follicles are shed. At the same time the 

 dense dermis shows vascular and cellular changes and is sloughed down to the 

 dermal fat layer after about fourteen days. The panniculus carnosus tends to 

 be perfectly normal, though in response to the developing superficial ulcer 

 there is a deep dermal vascular reaction with fibre formation. The ulcer heals 

 after about thirty days but the scar is thin-fibred, cellular and served by 

 dilated and insufficient blood vessels. These changes lead to hyalinization of 

 the scar which in turn is shed and this time the panniculus carnosus may be 

 partly shed too. Subsequent scarring again leads to the formation of an ulti- 

 mately acellular, avascular hyalinizing scar which lyses and breaks down. 

 After repeated cycles of ulceration and regeneration carcinomatous changes 

 are seen at the periphery of the lesion among the immigrating epidermal cells. 

 Most, if not all, of the exposed cells of the epidermis and hair foUicles are shed 



