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Biomedical subjects

W W Chang

Publications and source records attributed to W W Chang.

At least 55 records · Page 3Linked to original sources

Histogenesis of symmetrical 1,2-dimethylhydrazine-induced neoplasms of the colon in the mouse.

CF-1 female adult mice were given weekly sc injections of 20 mg symmetrical 1,2-dimethylhydrazine (DMH)-2HCl/kg body weight and killed at various intervals after commencement of the injection. [3H]thymidine (TdR) was given before the animals were killed. The histogenesis of colon neoplasms was investigated by means of autoradiographs prepared from sections of Epon-embedded descending colon, which were stained with periodic acid-Schiff reaction and iron hematoxylin. By 9 weeks after initiation of DMH treatment, the distal 5 cm of the colon became enlarged, the mucosa thickened, and the crypts were elongated and hyperplastic. In the hyperplastic crypts, the number of proliferating cells increased, but the distribution of these cells followed a previously discussed slow cut-off model of Cairnie et al. as for the normal crypts. Differentiation and transformation of epithelial cells occurred, but somewhat aberrantly. Hyperplasia of the crypts occurred diffusely, but neoplastic lesions that began to appear by 9 weeks after the intiial treatment were isolated. An isolated crypt from which a neoplasm developed was first repopulated by what appeared to be altered, undifferentiated "stem" cells. These cells did not differentiate, continued to divide, and eventually upon migration accumulated in the upper part of the crypts, where an earliest identifiable neoplastic lesion was observed. Once such a lesion was formed, it expanded in various directions, depending on the local environments, and formed a polypoid or discoid lesion. The biologic behavior of the neoplasm seemed to be determined by the downward progression of its leading edge. When it penetrated the muscularis mucosae, the neoplasm became highly invasive. In the murine model, the invasive adenocarcinomas were observed by 26 weeks after commencement of DMH treatment.

Adenocarcinoma↗

Inhibition of DNA synthesis by 1,2-dimethylhydrazine and methylazoxymethanol acetate in rabbit colon mucosa in organ culture.

When maintained in organ culture, colon mucosa from male New Zealand White rabbits showed a near-normal mucosal morphology and linear incorporation of [3H]thymidine into mucosal DNA up to 36 hours of incubation. Explants from the descending colon had a higher DNA synthetic activity than did other segments of the large bowel. Inhibition of DNA synthesis in colon explants by 1,2-dimethylhydrazine (DMH) and methylazoxymethanol (MAM) acetate was dose-dependent. When DNA synthesis was determined after an 18-hour incubation, MAM acetate inhibited DNA synthesis at concentrations of 50, 100, 150, and 200 microgram/ml. With the same concentration of DMH, little or no inhibition was observed. At the concentration of 200 microgram/ml, both carcinogens significantly inhibited DNA synthesis after 3 and 6 hours of incubation. With longer incubation, the inhibitory effect of DMH appeared to be reversible, whereas DNA synthesis was continuously inhibited by MAM acetate up to 18 hours of incubation. No altered uptake of [3H]thymidine by colon explants incubated in the presence of DMH or MAM acetate for 18 hours was observed. No morphologic changes were seen in colon explants treated with 200 microgram MAM acetate/ml for 18 hours. Physostigmine sulfate had no influence on MAM acetate-induced inhibition of DNA synthesis in colon explants. These in vitro observations reflected a direct action of DMH and MAM acetate on the colon mucosa and supported the possibilility that colon epithelial cells contain enzymes capable of activating DMH and MAM acetate to their alkylating carcinogens.

Animals↗

Effect of neonatal sympathectomy on the postnatal differentiation of the submandibular gland of the rat.

Right superior cervical sympathectomy was performed in one-day old rats. This operation had a small but definite effect on the postnatal development of the submandibular gland. The gland on the sympathectomized side weighed less and contained smaller amounts of DNA, RNA and protein than the contralateral intact gland. The postnatal development of acinar cells and granular convoluted ductal cells was retarded in the sympathectomized gland. The acinar cells which differentiated after the ganglionectomy were smaller than those in the contralateral intact gland and were filled with secretory granules but devoid of basal basophilia. The rate of cellular proliferation in the sympathectomized gland was, however, similar to that intact gland at various ages studied.

Animals↗

Pentagastrin stimulates epithelial cell proliferation in duodenal and colonic crypts in fasted rats.

In fasted rats, single injection of pentagastrin (250 mug/kg) stimulates epithelial cell proliferation in the duodenum and colon, but not in the esophagus. Fasting for 64 hours suppresses cell proliferation more markedly in colonic crypts than in duodenal crypts, and pentagastrin restores the cell proliferative activity of the colon and duodenum to levels comparable with those of fed rats. In both duodenal and colonic crypts, differentiating-proliferative cells in the mid-portion of the crypts are more responsive to pentagastrin stimulation than immature proliferative cells at the base of the crypts. Non-dividing epithelial cells are not affected. Pentagastrin has no influence on cell proliferation in fed rats.

Animals↗

Renewal of the epithelium in the descending colon of the mouse. IV. Cell population kinetics of vacuolated-columnar and mucous cells.

Proliferation and migration of cells in the vacuolated-columnar and mucous cell lines were studied in the descending colon of adult female mice given a single injection or a continuous infusion of 3H-thymidine and killed at various intervals from one hour to 12 days. This investigation was carried out using one mum-thick Epon sections which were radioautographed after staining with the periodic acid-Schiff technique and iron-hematoxylin. In the normalized crypts with ten equal segments, labeled vacuolated cells at one hour after injection of 3H-thymidine were encountered in the lower four segments and in decreasing numbers in segments 5 through 7. From the percent labeled cells in segments of the crypt, the birth rate and fluxes of cells were computed. Moreover, it was found that a cell in the vacuolated-columnar cell line would undergo three mitotic cycles on the average from its birth at the cryptal base to its extrusion from the surface; of these three cycles, the last one which took place from segment 3 to segment 7 appeared to be a changeover from dividing cells to non-dividing cells, in accordance with the "slow cut-off" model of Cairnie et al. ('65b). Mucous cells located in segments 1 through 6 of the crypt were capable of incorporating 3H-thymidine and thus capable of undergoing mitosis. However, the rate of turnover of mucous cells based on proliferative rate was found to be much lower than the rate of turnover of mucous cells based on the transit time in the non-dividing segments of the crypt. Since there was a concomitant overproduction of cells in the vacuolated cells and newly formed mucous cells in the lower portion of the crypt, it was concluded that some vacuolated cells would give rise to mucous cells. This putative transformation occurred in the lower four segments of the crypt. Mucous cells which were formed by transformation would migrate upward along the cryptal wall and accumulate more mucus in the theca; in doing so, they would undergo two divisions, on the average, before they became non-dividing mucous cells. In ascending the cryptal walls, both vacuolated-columnar cells and mucous cells appeared to migrate at a similar speed; they moved much slower at the base of the crypt and accelerated toward the upper portion of the crypt, but they migrated at a constant speed in the non-dividing segments of the crypt.

Animals↗

The development of the granular convoluted duct in the rat submandibular gland.

The development of the granular convoluted duct in the submandibular gland of male rats, 4 to 12 weeks of age, was investigated. During this period, the average weight of the gland increased from 213 to 526 mg, the total DNA and RNA contents doubled, and the protein content tripled. Radioautographs were prepared from Epon embedded sections of the gland of the rats given 3-H-thymidine and stained with toluidine blue. The glands of 4-week-old rats consisted mainly of acinar cells (45%), intercalated ductal cells (20%) and striated ductal cells (16%). A few granular convoluted ductal cells were seen in the striated duct close to the intercalated duct. The frequency (and absolute number) of granular convoluted ductal cells increased linearly from 1% (3 X 10-6) at four weeks to 26% (68 X 10-6) at eight weeks, while the calculated number of striated ductal cells remained stationary. The absolute number of acinar cells and intercalated ductal cells nearly doubled between four to eight weeks of age. The proliferative activity of all cell types declined with age but between six and ten weeks of age the rate of proliferation of ductal cells was relatively higher than the rate of proliferation of the acinar cells. Morphologically the size and number of granules in the granular convoluted ductal cells increased with age. Based on the above data it is concluded that the granular convoluted ductal cells developed from that segment of the striated ductal cells which is in close proximity with the intercalated ductal cells. The heterogeneity of the granules in the granular convoluted ductal cells observed from six weeks of age might denote the functional diversity of the cells.

Age Factors↗