Patterns of growth and ribosome accumulation during 3-methylcholanthrene-induced epidermal hyperplasia.

The growth of mouse epidermis following a single topical application of 1, 2, or 4 /¿moles 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 accumula tions of epidermal wet weight and protein and increases in the numbers of suprabasal cells and nucleated cell layers; the epidermis was also hyperkeratotic. Ribosome accumu lation preceded epidermal growth. Total ribosomal RNA per cell was increased 2to 3-fold 1 day after all doses of MCA. All doses elicited the same maximum cellular accumulation of ribosomes (3.5to 4.5-fold) at Days 4 to 7. The accumula tion 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 mem brane-bound ribosomes did not change from normal follow ing 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 /¿molesMCA. These results are interpreted as an integrated sequence of cell damage and loss, ribosome accumulation, and regenerative growth.