Abstract
The behaviour of the normal epidermis of mice on the first 5 days of exposure to a single application of carcinogens and cocarcinogens has been investigated by simple quantitative measurements of cell population, size of cells and thickness of the epidermis. Irritant substances and promoting agents both produce cellular hypertrophy but the respective responses can be distinguished by the much greater incidence of degenerate cells associated with irritant treatment. Urethane treatment is characterized by induction of a transient hypoplasia which is not in agreement with the level of cellular division. This response has also been demonstrated after treatment with mild carcinogens or low doses of potent carcinogens. Higher dose levels are followed by a reduction in the mitotic index after about 27 hours. The possibility of developing a preliminary screening test for carcinogenic substances is discussed in the light of these observations.
Highlights
SUMMARY.-The behaviour of the normal epidermis of mice on the first 5 days of exposure to a single application of carcinogens and cocarcinogens has been investigated by simple quantitative measurements of cell population, size of cells and thickness of the epidermis
Mottram (1944) and Berenblum and Shubik (1947, 1949) proposed a two-stage mechanism for carcinogenesis and it is generally accepted that initiation brings about some form of cellular change which remains latent until it is subsequently forced to appear as a tumour by persistent exposure to a promoting agent, Pure initiating agents are known and these when applied to the skin appear to have no visible effect upon the epidermis (Roe and Salaman, 1955), but the promoting stage is thought to be characterized by induction of a marked and sustained hyperplasia brought about by stimulation of cell proliferation and distinct from a regenerative hyperplasia (Setala, 1956; Salaman, 1961; Frei and Stephens, 1968)
The mice were obtained from Imperial Chemical Industries Ltd., and only 3 month old male mice were used because mitotic index is thought to vary with age (Bullough, 1949), the hair cycle is believed to be in the resting phase at this age (Andreasen, 1953) and mitotic index is believed to be associated with the oestrous cycle in female mice (Bullough, 1946)
Summary
SUMMARY.-The behaviour of the normal epidermis of mice on the first 5 days of exposure to a single application of carcinogens and cocarcinogens has been investigated by simple quantitative measurements of cell population, size of cells and thickness of the epidermis. Mottram (1944) and Berenblum and Shubik (1947, 1949) proposed a two-stage mechanism for carcinogenesis and it is generally accepted that initiation brings about some form of cellular change which remains latent until it is subsequently forced to appear as a tumour by persistent exposure to a promoting agent, Pure initiating agents are known and these when applied to the skin appear to have no visible effect upon the epidermis (Roe and Salaman, 1955), but the promoting stage is thought to be characterized by induction of a marked and sustained hyperplasia brought about by stimulation of cell proliferation and distinct from a regenerative hyperplasia (Setala, 1956; Salaman, 1961; Frei and Stephens, 1968) The purpose of this investigation was to examine the progress of the response after treatment with carcinogens, cocarcinogens and irritant substances using quantitative techniques in order to be as objective as possible. A distinction between the response to a non-carcinogenic irritant and the response to a promoting agent has been demonstrated but because the evidence is based on only a few experiments it is not certain whether this distinction can yet be regarded as applying generally
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