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Previously performed short-term (4-month) studies demonstrated that vitamins C and E, β-carotene and selenium modulate growth of early putative preneoplastic acinar lesions induced in rat pancreas by azaserine. The present paper summarizes the results of long-term studies performed with azaserine-treated rats maintained on diets high in either β-carotene, vitamins C and E or selenium. It appeared that rats given a diet high in β-carotene, vitamin C or selenium, but not vitamin E, developed fewer pancreatic tumours than controls. The chemopreventive effects of these micronutrients were most pronounced when β-carotene and/or selenium were given during the promotion phase of the carcinogenic process. Surprisingly, cell proliferation in azaserine-induced preneoplastic acinar lesions was higher in rats given β-carotene and/or selenium via the diet in comparison to controls. It is considered unlikely that any antioxidant alone can be associated with protection against cancer. It is concluded that dietary supplementation of combinations of antioxidants may have practical application in chemoprevention of cancer. Copyright (C) 1999 Elsevier Science Ltd.

Estrogen-induced pituitary lesions in rats were studied in time-sequence experiments using magnetic resonance imaging (MRI), hormone determinations and light microscopy. The main purpose of the study was to evaluate the usefulness of MRI in comparison with conventional biochemical and histopathological methods for detecting the pituitary lesions as early as possible and to follow their development. Measurements were made at 15 time points, ranging from 1 h to 272 days after s.c. implantation of the estrogen pellet. High-resolution T1 weighted sagittal images with 2 mm slice thickness were made with a 2 Tesla 30 cm small-bore MRI system. Radioimmunoassay (RIA) was used to determine the different pituitary hormones. Convential histopathology and immunoperoxidase staining methods were used to characterize the pituitary lesions and visualize the hormone-producing pituitary cells respectively. The first histopathological pituitary changes (enlarged acidophilic cells with increased number of vacuoles) were seen at day 2 after initiation of the estrogen treatment, while at day 4 the first immunohistochemical changes (increased number of prolactin-positive cells) were encountered. Significantly increased prolactin levels in blood plasma occurred from day 9 onwards. Also at day 9, changes of the pituitary gland were first visible on MR images, showing rounding of the anterior edge of the gland. Gradual enlargement of the pituitary caused by hyperplasia of hypertrophic prolactin-positive cells could be followed by MRI, and later on pituitary tumors were recognized, their images being heterogeneous due to great differences in signal intensity ranging from hypo- or iso- to hyperintense. Signal intensities of hemorrhagic tumor areas varies widely due to variation in the blood flow maintained in these areas. It was concluded that MRI is a powerful tool for detecting enlargement and tumors of the pituitary gland in rats. This method allows the development of such lesions to be followed in one and the same animal, thereby reducing the need of interim kills and thus the number of animals to be used. Chemicals/CAS: prolactin, 12585-34-1, 50647-00-2, 9002-62-4; Estradiol, 50-28-2; Estrogens; Pituitary Hormones