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Patterns of Growth and Ribosome Accumulation during 3-Methylcholanthrene-induced Epidermal Hyperplasia¹

Department of Biology, Syracuse University [S. N. M.], and Department of Pathology, State University of New York, Upstate Medical Center, Syracuse, New York 13210 [T. S. A.]

The growth of mouse epidermis following a single topical application of 1, 2, or 4 µmoles 3-methylcholanthrene (MCA) to the back of a mouse and the pattern of ribosome accumulation associated with this growth were quantitated. All doses of MCA produced cell hypertrophy, cell damage, and basal cell loss, and increased intercellular spacing within 3 days; the extent and duration of these effects were increased with increasing dose. There followed accumulations of epidermal wet weight and protein and increases in the numbers of suprabasal cells and nucleated cell layers; the epidermis was also hyperkeratotic. Ribosome accumulation preceded epidermal growth. Total ribosomal RNA per cell was increased 2- to 3-fold 1 day after all doses of MCA. All doses elicited the same maximum cellular accumulation of ribosomes (3.5- to 4.5-fold) at Days 4 to 7. The accumulation of ribosomes was disproportionate in that it exceeded by over twofold the accumulation of protein and DNA per unit area of epidermis. The proportions of free and membrane-bound ribosomes did not change from normal following treatment (85% free:15% membrane-bound). Ribosome content remained elevated while the epidermis was hyperplastic; it returned toward normal levels as the epidermis approached its normal appearance. All variables measured were at normal levels 21 days after 2 µmoles MCA. These results are interpreted as an integrated sequence of cell damage and loss, ribosome accumulation, and regenerative growth.

¹ This work was supported by Grants AM 18219-01 and RR-5402 from NIH and a grant from the Syracuse University Graduate School.

² Work performed in partial fulfillment of the requirements for the Ph.d. in Biology in the Graduate School of Syracuse University, Syracuse, N.Y. Present address: The Wistar Institute of Anatomy and Biology, 36th Street at Spruce, Philadelphia, Pa. 19104. To whom requests for reprints should be addressed.

Received 12/14/76. Accepted 6/ 6/77.