INDEX epithelial cells

Colquhoun and Schumacher [98] have shown that y-linolcnic acid and eicosapentaenoic acid, which inhibit Walker tumor growth in vivo, decreased proliferation and apoptotic index in these cells. Development of apoptosis was characterized by the enhancement of the formation of reactive oxygen species and products of lipid peroxidation and was accompanied by a decrease in the activities of mitochondrial complexes I, III, and IV, and the release of cytochrome c and caspase 3-like activation of DNA fragmentation. Earlier, a similar apoptotic mechanism of antitumor activity has been shown for the flavonoid quercetin [99], Kamp et al. [100] suggested that the asbestos-induced apoptosis in alveolar epithelial cells was mediated by iron-derived oxygen species, although authors did not hypothesize about the nature of these species (hydroxyl radicals, hydrogen peroxide, or iron complexes ). 

Extensive destruction of the olfactory epithelium was observed in male Fischer 344 rats exposed to 200 ppm [780 mg/m ] methyl bromide for 6 h per day for five days. By day 3, despite continued exposure, there was replacement of the olfactory epithelium by a squamous-cell layer, followed by progressive reorganization toward the normal architecture, and by week 10,75-80% of the epithelium appeared histologically normal. Olfactory epithelial-cell replication was maximal on day 3 of exposure, with a labelling index of 14.7% compared with 0.7% in the controls (Hurtt et al., 1988). Degeneration and subsequent regeneration were also observed in an inhalation experiment w ith Fischer 344 rats exposed to 175 ppm [680 mg/m ] 6 h twice, separated by a 28-day interval (Bolon et al., 1991). 

Chan P, Chapman JR, Morris PJ. Glycosuria an index of cyclosporine nephrotoxicity. Transplant Proc 1987 19 1780. Nakahama FI. Stimulatory effect of cyclosporine A on endothelin secretion by a cultured renal epithelial cell line, LLC-PK1 cells. Eur J Pharmacol 1990 180 191-192. 

Other studies have also directly compared the antifungal and toxic effects of the two formulations to confirm a wider therapeutic index. A greater toxicity to kidney epithelial cell structures of AmB was apparent when compared with AmB in DMPC DMPG liposomes. LLC-PKl renal cells, exposed to short exposure times (2 hours), with different formulations of DMPC DMPG liposomes, exhibited different EC5q s, the most potent having an EC5Q 13 times that of AmB... 

The plasminogen activation assay is based on the release of plasminogen activator from primary rabbit corneal epithelial cells as a quantitative index of toxicity. A high conrclalion between plasminogen activation and known in vivo eye irritating potential was demonstrated by Bagley etal. (1994). 

Several small intervention trials have used indices of colorectal epithelial cell proliferation as intermediate endpoints. Supplementation with 3g/d of vitamin C for at least 18 months resulted in a significantly decreased proliferation index in rectal epithehal cells compared with placebo in patients with FAP " " In another small trial, supplementation with 750mg/d of vitamin C or 9mg/d of p-carotene but not 160mg/d of vitamin E for one month decreased cell proliferation in colonic crypts of adenoma patients compared with the baseline. However, supplementation of colorectal adenoma or colorectal cancer patients with 30mg/d of p-carotene for 3 months decreased indices of colonic cell proliferation when compared with a placebo. A stndy of colon cancer patients randomized to receive a combination of lOOOmg/d of vitamin C, 70mg/d of a-tocopherol, 30,000 lU/d of vitamin A, and 2000mg/d of calcinm or placebo for 6 months... 

For light microscopy, the fetal thyroid gland was fixed in 10% buffered formalin solution after weighing. Tissue blocks were embedded in paraffin. Sections were stained with HE and PAS. Frozen sections were stained for peroxidase activity. In addition to the routine microscopic examination, the maximal diameter of the follicles and the heights of the epithelial cells and their nuclei were measured by micrometer. In each case, 100 cells were randomly measured, the average values were obtained and the nucleus-cytoplasm index (N/C) was calculated. 

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