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Biomedical subjects

G Shklar

Publications and source records attributed to G Shklar.

At least 73 records · Page 4Linked to original sources

Acute effect of DMBA application on mitotic activity of hamster buccal pouch epithelium.

One, two, or three applications of a 0.5% solution of DMBA in mineral oil were made to the buccal pouches of three groups of hamsters. There were 10 animals in each group, and additional groups of 10 animals were used as mineral oil controls. Mitotic activity was studied in epithelial whole mounts of buccal pouch following intraperitoneal injection of vinblastine (VBL) in a dose of 4 mg per kilogram of body weight 4 1/2 hours, 24 hours, 48 hours, 1 week, and 2 weeks after treatment. Similar groups of animals were used for a thymidine-labeling experiment. Immediately after the last DMBA application to buccal pouches, 3H-TdR was injected intraperitoneally in a dose of 1 microcurie per gram of body weight. All labeling was studied autoradiographically in epithelial whole mounts of buccal pouches stained with hematoxylin. A cell with five or more grains of label per nucleus was considered labeled. It was found that with one application of DMBA mitotic activity, as studied after VBL injection, was greatly reduced during the experimental period of 2 weeks. After two DMBA applications there was a significant reduction in mitotic activity in the first 48 hours but a return to normal by 2 weeks, indicating a reaction to the damage produced by the two DMBA applications. The thymidine-labeling study tended to confirm this result. The label in the animals that received two DMBA applications disappeared after 48 hours, indicating increased mitotic activity and tissue repair, while animals with one DMBA application maintained the label after 1 week.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of vitamin E dietary supplements on the exposed dental pulp in rats.

Forty adult male Sprague-Dawley rats were divided into two equal groups, control (Group 1) and experimental (Group 2). Group 2 received 100 mg of dl-alpha-tocopherol acetate (vitamin E) twice weekly by the oral route. After 2 weeks the animals in both groups were subjected to pulp exposures that were capped with zinc oxide and eugenol and to pulp exposures that were left open. The oral administration of 100 mg dl-alpha-tocopherol acetate in the Group 2 animals was continued for periods of 1 day to 4 weeks after the operative procedures. The animals were killed 1 day, 3 days, and 1, 2, and 4 weeks after the procedures. The most severe, prolonged, and extensive pulpal disease was seen in both groups when the pulp exposure was left open to the oral flora. The most favorable repair and healing results took place after 1, 2, and 4 weeks in the Group 2 animals in pulp exposures covered with zinc oxide and eugenol.

Animals↗

Effects of smokeless tobacco and snuff on oral mucosa of experimental animals.

The effects of smokeless tobacco on oral mucosa were studied in 60 Syrian hamsters. Histologic study of the buccal pouch mucosa revealed no significant pathologic changes at either ten or 20 weeks after the start of the experiment. However, studies on epithelial whole mounts revealed a statistically significant decrease in mitotic activity and a statistically significant increase in the number of Langerhans' cells in animals subjected to daily use of tobacco or snuff for 20 weeks.

Animals↗

RA can alter the distribution of ATPase-positive Langerhans cells in the hamster cheek pouch in association with DMBA application.

Thirty-six young adult male and female Syrian hamsters were divided into four groups. Group 1 (N = 6) was treated with mineral oil, Group 2 (N = 12) was treated with 7,12-dimethylbenz[a]anthracene (DMBA), Group 3 (N = 12) was treated with DMBA and 13-cis-retinoic acid (RA), and Group 4 (N = 6) was treated with RA only. The hamsters were treated three times a week for six weeks. When the DMBA-treated animals were also treated with RA, tumor formation was inhibited. In the DMBA-treated animals that did not have RA, there was a significant reduction in the number of Langerhans cells (LCs) located interfocally and in foci compared with controls (p less than or equal to 0.001). The systemic administration of 10 mg of RA significantly increased the number of ATPase-positive LCs in the focal aggregates (p less than or equal to 0.001). Interfocally, the number of ATPase-positive LCs was statistically elevated in pouches from RA- and DMBA-treated animals (Group 2 vs. Group 3, p less than or equal to 0.01). Following the administration of RA (Group 4), there was a statistically significant increase of LCs interfocally compared with Groups 2 or 3 (p less than or equal to 0.001). RA administered alone resulted in a small increase in foci compared with Group 3 but in a significant decrease compared with the control group (p less than or equal to 0.001). Systemic RA appears to not only affect the number of ATPase-positive LCs but also to alter the distribution of these cells in DMBA-treated pouches.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

Alpha tocopherol alters the distribution of Langerhans cells in DMBA-treated hamster cheek pouch epithelium.

Thirty-seven adult male and female golden hamsters (Mesocricetus auratus) were divided into four experimental groups. In Group A, the animals served as untreated controls, having the left buccal pouches painted with mineral oil. In Group B, the animals received 10 mg vitamin E (alpha tocopherol) in peanut oil by the oral route, with a fine pipette, twice weekly. In Group C animals, the left buccal pouch was painted three times weekly with DMBA (0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil). Group D animals received both vitamin E and DMBA in the amounts indicated for Groups B and C, with the vitamin E being administered on days alternate to the DMBA painting, also in the manner described for the above groups. All animals were killed after eight weeks of treatment. Epithelial whole mounts were prepared from the left buccal pouches. These specimens were then stained for ATPase to demonstrate the presence of Langerhans cells (LCs). A notably decreased density of LCs was observed after treatment with DMBA. Vitamin E administration in addition to DMBA treatment resulted in a less dramatic decrease in LC density. Since vitamin E has been shown to retard experimental oral carcinogenesis, vitamin E may retard carcinogenesis by maintaining the number of Langerhans cells.

9,10-Dimethyl-1,2-benzanthracene↗

Healing of spontaneous periodontal defects in dogs treated with xenogeneic demineralized bone.

This study was undertaken to histologically, clinically and radiographically evaluate the sequence of healing following implantation of bovine demineralized bone powder (DBP) into severe, spontaneous periodontal defects in beagle dogs. Eight dogs with documented severe periodontitis were treated surgically following initial debridement. One quadrant in each arch was treated with conventional flap surgery and the others were treated with surgery followed by DBP implantation. Animals received postoperative debridement and clinical and radiographic evaluation. Two dogs were sacrificed at 1, 3, 6 or 12 months postoperatively, and the jaws were evaluated histologically. Clinically, DBP was well tolerated by recipients. No evidence of localized inflammatory response or delayed hypersensitivity reaction was noted. Significant reductions in gingival inflammation were noted in both experimental and control sites at 1 month postoperatively compared to preoperative scores. Equivalent periodontal pocket reduction was noted between test and experimental sites and remained significant at 12 months. Radiographically, no differences were noted in the rate of bone loss between control and test sites. Histologic evaluation demonstrated the presence of DBP at 1 month following implantation, but the material was replaced with new bone by the next sacrifice period. Periodontal ligament fibers of standard orientation were seen extending from DBP-induced bone to the root surface by 1 month after implantation. An intact epithelial attachment appeared to be present 1 month after the implantation of DBP. No differences in root surfaces were detected between test and control groups. Ankylosis was a rare finding, noted equally between test and control sites. DBP did not appear to predispose to external root resorption. In later stages, histologic evidence of advancing periodontitis was noted equally in both control and experimental groups. While DBP successfully induced new bone formation, the inability to adequately maintain the periodontal tissues due to bacterial accumulation in this model combined with recurrent pocket formation, precluded any conclusion regarding long-term advantage. Based on these findings, clinical trials of this or similar materials are recommended.

Alveolar Process↗

A histologic study of epithelial dysplasia in oral lichen planus.

One hundred cases of oral lichen planus were reviewed together with 100 nonspecific oral mucosal inflammatory lesions as a control group. The presence of dysplasia was noted, using well-established histologic criteria. Mild dysplasia was found in 57% of cases, moderate dysplasia in 9%, and severe dysplasia in 2% of cases. In the control group, mild dysplasia was observed in 32% of cases, moderate in 10%, and severe dysplasia was not present. It is suggested that, while mild or moderate dysplasia may not indicate precancerous potential, severe dysplasia in lichen planus may signify the development of a precancerous lesion.

Adult↗

Initiation and promotion in experimental oral carcinogenesis.

A subthreshold dose of 0.1% DMBA in oil applied to hamster buccal pouch three times a week for 10 weeks did not result in the development of carcinoma in up to 25 weeks from the start of the experiment. However, if the subthreshold dose of DMBA was followed by 6 weeks of no treatment and six weeks of 40% benzoyl peroxide treatment, carcinomas developed rapidly. Both benzoyl peroxide and its acetone solvent are noncarcinogenic. An experiment carried out on sixty-six young adult male and female Syrian hamsters demonstrated these results, using appropriate controls.

9,10-Dimethyl-1,2-benzanthracene↗

Acute effect of DMBA application on Langerhans cells of the hamster buccal pouch mucosa.

One, two, and three applications of DMBA in mineral oil to hamster buccal pouch mucosa did not result in obvious histologic alterations in experimental periods ranging from 4 1/2 hours to 2 weeks after the last DMBA application. However, there were significant increases in the number of Langerhans cells, as disclosed histochemically with ATPase staining. There was also an increase in the length and size of the dendritic processes of the Langerhans cells. Applications of DMBA in oil resulted in a consistently significant increase in Langerhans cells when compared to the buccal pouch mucosa of untreated animals. However, mineral oil applications also resulted in a slight increase in Langerhans cells when compared to the mucosa of untreated controls. The major effects of the DMBA on Langerhans cells occurred after 2 weeks and with increasing numbers of applications. The increase in Langerhans cells is interpreted as an enhanced response by immunologically competent cells which may represent an early immune response to the very early changes in carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Retardation of experimental oral cancer by topical vitamin E.

Forty-eight young male and female golden hamsters (Mesocricetus auratus) were divided into four groups of 12 animals each. The left buccal pouches of Group 1 and 2 animals were painted 3 times weekly with a 0.5% solution of 7,12-dimethylbenz(a)anthracene (DMBA) in heavy mineral oil for 7 weeks. At the end of this period, the left buccal pouches of Group 2 animals were painted 3 times weekly with vitamin E (DL-alpha-tocopherol, in pure form) for an additional 4 weeks. Group 3 animals were painted with vitamin E only, for 4 weeks. Group 4 animals were untreated controls. Group 2 animals demonstrated a significant delay in tumor formation in comparison with Group 1 animals. Gross observation revealed fewer and smaller tumors in the Group 2 animals; microscopic examination revealed smaller tumors with better cellular differentiation and less invasion. No tumors were observed in Group 3 and Group 4 animals. These observations were similar to those made in previous studies of oral carcinogenesis using systemic vitamin E to delay tumor formation.

9,10-Dimethyl-1,2-benzanthracene↗

The effect of chemically induced oral carcinomas on peritoneal macrophages.

Peritoneal macrophages derived from normal and 7,12-dimethylbenz(a) anthracene (DMBA) treated, tumor bearing, Syrian hamsters were isolated and characterized. Peritoneal exudate cells from tumor bearing animals as compared to normal controls, showed that there was an increase in the total number of cells in the exudate. Specifically, there was an increase in macrophages as compared to other cell types. In terms of their cytochemical functions, these macrophages demonstrated a reduction in histochemical activity and functional capacity (Fc and C3 receptors), and cytotoxic specific lysis of DMBA squamous cell carcinoma tumor targets. There was also a significant increase in adherence and the number of resident macrophages as opposed to exudate macrophages of the peritoneal macrophages. These results seem to indicate an alteration in functional and cytochemical activity of macrophages derived from a hamster with a growing cheek pouch tumor induced by DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of estradiol on ultrastructure of granular ducts in submandibular glands of female rats.

The effects of estradiol on the granular ducts in submandibular glands of female albino rats were studied. Twenty-five-milligram pellets of 17 beta-estradiol were implanted subcutaneously in the experimental animals, and their glands, as well as controls, were examined after 2, 4, 7, and 10 wk using light and electron microscopy. During the course of the experiment an increasing proportion of the granules in the granular ducts appeared more lightly stained in the experimental animals. In the estradiol-treated rats the granular ducts increased in relative cross-sectional area at a faster rate than in the controls, which exhibited maturation changes. In addition, the average number of granules per granular duct cell decreased significantly in the treated animals. Our results indicate that estradiol caused a change in the cytology of the granular ducts suggesting an alteration in protein synthesis. These results might occur through a change in structural proteins or in other hormones and growth factors which are known to influence the submandibular gland.

Animals↗

Oral mucosal tumor inhibition by ibuprofen.

Eighty young adult male and female golden hamsters (Mesocricetus auratus) were divided into four equal groups. The left buccal pouches of the animals in group 1 were painted three times weekly for 24 weeks with 0.1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in heavy mineral oil. The left buccal pouches of the animals in group 2 were similarly painted with DMBA for 24 weeks, but the animals also received 10 mg ibuprofen (Motrin) administered systemically by the oral route twice weekly. The animals in group 3 received only ibuprofen, and those in group 4 served as untreated controls. After 24 weeks the animals were killed in groups of 16 (two males and two females from each of the four experimental groups) per week and their left buccal pouches studied for the presence of tumors. Sizes of tumors were also recorded. Ibuprofen was found to prevent tumor formation at 25-27 weeks. Some tumors developed in the animals receiving DMBA and ibuprofen by the 28-29 week, but they were fewer in number and smaller than those of the animals receiving only DMBA and not ibuprofen.

9,10-Dimethyl-1,2-benzanthracene↗

Retardation of experimental oral cancer development by retinyl acetate.

Sixty young adult Syrian hamsters were divided into five groups. Group 1 and Group 2 animals were treated with 0.25% dimethylbenz(a)anthracene (DMBA), painted on their left buccal pouches thrice weekly for 20 weeks. Starting at 12 weeks, at which time there was clinical evidence of leukoplakia and initial tumor formation, Group 2 animals received 10 mg retinyl acetate 3 times/week in a 5% solution in peanut oil, while Group 1 animals received only peanut oil. Two animals in Group 1 and two animals in Group 2 were sacrificed weekly from week 12 to week 20. Left buccal pouches were examined, tumors were counted, and tumor size was measured. Group 3 animals were untreated controls, Group 4 animals were retinyl acetate controls, and Group 5 animals received only peanut oil. It was found that DMBA-treated animals receiving retinyl acetate from week 12 to week 20 developed fewer tumors, and their average tumor size was less than that in DMBA-treated animals not receiving retinyl acetate. It appears that retinyl acetate, administered systemically, can retard tumor development even after leukoplakia has been established and tumors have begun to develop.

9,10-Dimethyl-1,2-benzanthracene↗

The effect of vitamin E on the healing of gingival wounds in rats.

Forty male and female albino rats received a standardized gingival wound (gingivectomy) between the mandibular incisor teeth. One half of the animals received 60 I.U. of d-alpha-tocopheryl acetate daily, administered orally by pipette. An additional control group of 20 animals was not wounded and half of these animals received 60 I.U. of d-alpha-tocopheryl daily. Four animals in each of the two gingivectomy groups (Groups 1, 2) were sacrificed at periods of 1, 2, 4, 7 and 14 days following gingivectomy. Two animals in each of two control unwounded groups (Groups 3, 4) were sacrificed at similar times. Gingival healing was studied grossly and histologically. The animals receiving the vitamin E supplements healed more rapidly, with almost complete restoration of gingiva by 7 days. Complete healing was seen in both control and experimental groups by 14 days. Vitamin E was shown to accelerate gingival wound healing in experimental animals.

Animals↗

An epidermoid carcinoma cell line derived from hamster 7,12-dimethylbenz[a]anthracene-induced buccal pouch tumors.

w cell line, HCPC I, was established from an epidermoid carcinoma of the Syrian golden hamster cheek pouch. The carcinoma was induced by applications three times a week of a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in heavy mineral oil. The HCPC I cell line has been maintained through 60 passages over 15 months. Electron microscopy of the cell line revealed tonofilaments and desmosomes, thereby confirming its epithelial nature. Presence of keratin in the HCPC I cells was demonstrated by both histochemical and indirect immunofluorescence studies. The population-doubling time of HCPC I, estimated from the exponential growth phase of the growth curve established for the cell line, was 12 hours. The plating efficiency of the cell line was estimated at 35%. When an inoculum size of HCPC I, numbering 2.4 X 10(7) cells, was transplanted to the cheek pouch of an immunosuppressed inbred hamster, a papillary tumor, measuring 5 X 1 mm and microscopically diagnosed as a well-differentiated epidermoid carcinoma, developed 1 week post transplantation. Further successful transplantation was achieved with 1.8 X 10(7) HCPC I cells inoculated into the cheek pouch of a nonimmunosuppressed inbred hamster. A raised plaquelike mass, microscopically diagnosed as invasive epidermoid carcinoma, developed in the hamster cheek pouch 5 weeks post transplantation. Furthermore, 5 nonimmunosuppressed hamsters that received 1 X 10(6) HCPC I cells on their cheek pouches developed tumors microscopically diagnosed as anaplastic carcinomas 14 weeks post transplantation. The largest of these tumors measured 2 cm in diameter.

9,10-Dimethyl-1,2-benzanthracene↗