Ultrastructural analysis of the retinoid-induced reversal of epithelial hyperplasia and metaplasia.

The 7, 12-dimethylbenzanthracene-induced skin papilloma of the mouse and the 3-methylcholanthrene-induced hyperplasia and metaplasia in prostate organ cultures were studied by electron microscopy. The two types of tissue both showed a reversal of hyperplasia and metaplasia when treated with retinoids (= vitamin A and analogs). This reversal was reached by means that are quite characteristic for a given type of tissue. In the skin, DNA-synthetic activity was not influenced by retinoid treatment. There was however, considerable necrosis and an impressive mucous metaplasia. The latter might be at least partly responsible for the cell loss, probably through a loss of anchorage in the prickle-cell layer. In the prostate, no mucous metaplasia was observed, but there was an important depression of DNA-synthetic activity. The secretory apparatus reappeared together with the microvilli, possibly induced by the slowing down of cell division.

Interaction of retinoic acid and 3-methylcholanthrene on the fine structure of mouse prostate epithelium in vitro.

The effects of 3-methylcholanthrene (MCA) and retinoic acid (RA) on the fine structure of AKR mouse prostate epithelium in organ culture were correlated with changes in cell proliferation. In intact glands before explantation, the epithelial cytoplasm showed concentric flat or globular cisternae of endoplasmic reticulum in both supranuclear and basal areas, a well-developed Golgi complex, secretory vesicles, and numerous microvilli at the luminal surface. After explantation, the cytoplasmic organelles, particularly the endoplasmic reticulum, regressed and tonofilaments appeared. The regression was largely prevented by RA. MCA induced considerable epithelial hyperplasia and squamous metaplasia. The fine structure of the newly formed cells revealed a complete loss of endoplasmic reticulum, Golgi apparatus, secretory vesicles, and microvilli, with the appearance of bundles of tonofilaments and a striking increase in the number of desmosomes. Administration of RA to explants pretreated with the carcinogen partially reversed the hyperplasia and squamous metaplasia. The tonofilaments disappeared and the number of desmosomes greatly decreased, whereas endoplasmic reticulum, Golgi complex, secretory vesicles, and microvilli were largely reestablished. Planimetric measurements of the alveolar epithelium showed that the squamous transformation and its partial reversal by RA coincide with the rise and decline of epithelial hyperplasia. The data suggest that the restoration of secretory differentiation by RA was responsible for the initial breakdown of the hyperplastic epithelium, whereas the lowering of DNA synthesis by RA prevented further hyperplasia and kept cell replication within normal limits.

Localization of minor protein components of the head of bacteriophage T4.

The bacteriophage T4 capsid contains a number of minor proteins that are required for head assembly but whose detailed function and position in the head are unknown. We have found that by systematically varying the conditions of extraction, some of these minor proteins can be removed while the main capsid structure is left substantially intact. Electron microscopic examination of the residual capsids showed that the extraction of the product of gene 20 is correlated with the loss of a plug that distinguishes one vertex position (presumably the tail attachment site) from the others. Extraction of the product of gene 24 is correlated with the loss of the other 11 (nonproximal) vertexes of the capsid. We further show that antibody to P24 binds specifically to the nonproximal vertexes of both T4 preheads and T4 phages. On the basis of our findings, we suggest that P20 is located at or near the tail attachment site of the capsid, whereas P24 forms the 11 nonproximal vertexes of preheads and P24 forms the nonproximal vertexes of the mature head.