Abnormal cell proliferation and differentiation and urothelial tumorigenesis in essential fatty acid deficient (EFAD) rats

Abstract

Data provided by several investigators is showing conclusively that the mechanisms regulating normal proliferation and differentiation of certain cell populations are upset in EFAD rats. In most studies, a significant increase in the mitotic index was recorded. This has been seen in squamous keratinizing epithelia of the skin and upper alimentary tract (tongue, esophagus and forestomach). Also, an increase of cell proliferation was found in the gastric glands and intestinal crypts of the EFAD mice and rats. Study of the mitotic index of most organs of the EFAD rat is under investigation in our laboratory. Though, a more dynamic approach to evaluating changes in cell proliferation in EFAD such as was carried on by McCullough et al., 28 using cell labeling, will open leads for understanding the role of EFA and presumably their biological active products, such as prostaglandins, in controlling the cell cycle of various populations. Yet, it is apparent that most cell populations characterized by active renewal, and in which mitoses are normally abundant, such as covering epithelia 23 are particularly responsive to the EFAD condition. The recognition of urothelial tumors in a small, though significant number of EFAD rats, and the large incidence of atypical hyperplasias suggest that in this nutritional condition abnormal proliferation and tumorigenesis of the transitional epithelium (urothelium) of the urinary passages is favored. The study of the pathology, life span and longevity of the chronically EFA-deficient rat is showing that: (1) Proliferation and differentiation of certain cell populations are abnormal and, as for urothelial cells, neoplastic in nature and (2) these changes increase in frequency with aging.