Trickler D

Inhibition of hamster buccal pouch carcinogenesis by 13-cis-retinoic acid

Sixty-four male and female Syrian hamsters, 3 months of age and weighing 90 to 120 grams, were divided into four equal experimental groups. In animals of Groups 1 and 2 the left buccal pouch was painted three times weekly with a 0.5% solution of DMBA in heavy mineral oil. Group 2 animals also received 10 mg. of 13-cis-retinoic acid in peanut oil administered orally twice a week by pipette. Carcinogen retinoid were administered on alternate days. Group 3 animals served as controls, receiving only 13-cis-retinoic acid. Group 4 animals served as untreated controls. Four animals in each group (two males and two females) were killed at 10, 12, 14, and 16 weeks. The Group 2 animals, which received 13-cis-retinoic acid, exhibited a significant delay in DMBA carcinogenesis of buccal pouch mucosa, as studied both grossly and histologically. Both groups eventually demonstrated well-differentiated epidermoid carcinomas, but the tumors were smaller in the DMBA-retinoid animals.

Prevention of experimental oral cancer by extracts of Spirulina-Dunaliella algae.

An extract of Spirulina-Dunaliella algae was shown to prevent tumor development in hamster buccal pouch when a 0.1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil was applied topically three times weekly for 28 weeks. The algae extract was delivered by mouth in continued dosages of 140 micrograms in 0.4 ml mineral oil three times per week. After 28 weeks, the animals given vehicle and untreated controls all presented gross tumors of the right buccal pouch. Animals fed canthaxanthin presented a notably and statistically significant reduction in tumor number and size compared with controls. Animals fed beta-carotene demonstrated a smaller but statistically significant reduction in tumor number and size. The algae animals presented a complete absence of gross tumors. However, microscopic sections of the buccal pouch in the algae group showed localized areas of dysplasia and early carcinoma-in-situ undergoing destruction.

The effectiveness of a mixture of β-carotene, α-tocopherol, glutathione, and ascorbic acid for cancer prevention

Abstract Previous studies have shown that β‐carotene and α‐tocopherol can act synergistically to inhibit the growth of experimentally induced oral cancer. The initial studies on the synergistic anticancer activity of antioxidants have been extended to include reduced glutathione and ascorbic acid. Sixty male hamsters (4–5 wks old) were divided into six equal groups. Groups 1–6 were treated with 7,12‐dimethylbenz[a]anthracene (DMBA) (0.5% solution). Group 2 received a mixture containing equal amounts of β‐carotene, dl‐α‐tocopherol (vitamin E), glutathione, and l‐ascorbic acid (vitamin C) (12.5 μg) delivered orally by pipette. Groups 3–6 were treated with β‐carotene alone (50 μg), vitamin E alone (50 μg), glutathione (50 μg) alone, and vitamin C alone (50 μg). Animals were euthanized at 12 and 14 weeks. Tumors were counted and measured, and tumor burden was calculated for each experimental group. The mixture of antioxidants significantly reduced tumor burden, whereas the β‐carotene, vitamin E, and reduced g...

Regression of experimental cancer by oral administration of combined α‐tocopherol and β‐carotene

Abstract α‐Tocopherol (vitamin E) and β‐carotene have been shown to be capable of regressing established epidermoid carcinomas of hamster buccal pouch when injected locally into the tumor site. Neither has yet been shown to be effective in regressing cancer when adminstered by oral route. However, a combination of both α‐tocopherol and β‐carotene was shown to be effective in regressing epidermoid carcinomas of hamster buccal pouch when the mixture was adminstered orally in vegetable oil. The epidermoid carcinomas were induced in the right buccal pouch of 100 Syrian hamsters by painting three times weekly for 14 weeks with a 0.5% solution of 7,12‐dimethylbenz[a]an‐thracene in mineral oil. The animals were then divided into five equal groups of 20 animals. Group 1 animals received no further treatment and represented tumor controls. Group 2 animals received 200 μg β‐carotene and 200 μg dl‐α‐tocopherol acid succinate combined in 0.2 ml vegetable oil. Animals received the mixture daily by mouth using a 1 ‐ml ...

Retinoid inhibition of lingual carcinogenesis.

Sixty-four male and female Syrian hamsters, 3 months of age and weighing 90 to 120 grams, were divided into four equal experimental groups. In animals of Groups 1 and 2 the right posterior lateral border of the tongue was painted three times weekly with a 0.5 percent solution of DMBA in acetone. Group 2 animals also received 10 mg. of 13-cis-retinoic acid in peanut oil administered orally twice weekly by pipette. Carcinogen and retinoid were administered on alternate days. Group 3 animals received only 13-cis-retinoic acid. Group 4 animals served as untreated controls. Four animals in each group were killed at 12, 14, 16, and 18 weeks. The Group 2 animals, receiving 13-cis-retinoic acid, exhibited a significant delay in the development of lingual tumors, both grossly and microscopically. At 14 weeks carcinomas were found in the DMBA animals, but only dysplasia and areas of carcinoma in situ were found in the DMBA-retinoid animals. After 18 weeks the DMBA animals exhibited large lingual tumors with surfacenecrosis, while the DMBA-retinoid animals presented smaller tumors with less invasion of underlying tissue.

The administration of beta carotene to prevent and regress oral carcinoma in the hamster cheek pouch and the associated enhancement of the immune response.

In the past four years this laboratory has utilized the hamster cheek pouch tumor model to investigate the anticancer activities of antioxidants, such as beta carotene. These molecules, which have exhibited no evidence of toxicity, have been administered systemically (oral ingestion), and locally to the tumor site in the hamster cheek pouch. The results have been either the inhibition of tumor growth, or the regression of tumor. Adjacent to the degenerating tumors a dense inflammatory infiltrate was observed. Specifically, the cytokines, tumor necrosis factor alpha, and beta, have been immunohistochemically localized to the site of regressed oral carcinoma. Recently, liposomes composed of phosphaditylcholine, phosphaditylserine, and phosphodityelanolamine were combined with beta carotene and injected locally to oral squamous cell carcinoma of the hamster. The results indicated that tumor cells accumulated the liposomes and were lysed while normal mucosal cells did not demonstrate this effect. Therefore antioxidants such as beta carotene can be localized to a tumor site, without a toxic response. Future studies on the anticancer activity of the antioxidants need to focus on the cellular and molecular changes produced in the immune effectors and in the mucosal cells following administration of the antioxidants.

Inhibition of oral carcinogenesis by glutathione

Forty young adult Syrian hamsters (Mesocricetus auratus) were divided into four groups of 10 animals each. In Group 1 (tumor control), the right buccal pouches were painted three times per week with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in heavy mineral oil (USP) with a no. 4 sable brush. In Group 2 (experimental group), the right buccal pouches were painted with DMBA, as in Group 1. In addition, Group 2 received 1 mg of reduced glutathione in 0.5 ml of mineral oil three times per week on days alternate to the DMBA application. The glutathione was administered systemically by mouth with a pipette. Group 3 received only glutathione, and Group 4 was untreated (control groups). Animals were sacrificed after 14 weeks, and tumors were counted and measured. Both right and left pouches were photographed, excised, fixed in formalin, sectioned in paraffin, and studied histologically. The animals receiving glutathione demonstrated significantly fewer and smaller tumors. The mean tumor burden was 315 mm3 in the glutathione-treated group and 3,040 mm3 in the untreated group. The statistical significance by Students t test was < or = 0.0001. Histological study also revealed significantly fewer areas of dysplastic leukoplakia in the group treated with glutathione. This study represents the first demonstration of the anticancer effect of systemically administered reduced glutathione.

Directed lysis of experimental cancer by β-carotene in liposomes

Abstract The purpose of this study was to extend the knowledge of the antitumor activity of liposomes and to identify, for the first time, the antitumor effect of liposomes with the antioxidant β‐carotene. The administration of the carotenoid encapsulated in liposomes has the advantages of quantitation, facilitation, and most importantly an increased therapeutic response, resulting in the accentuation of regression of carcinoma in the hamster pouch. Tumors induced after the application of the carcinogen 7,12‐dimethylbenz[a]anthracene (0.5%) were injected with liposomes composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine in a ratio of 1:1:1 (large unilamellar vesicles). Tumor‐bearing animals were divided into four groups, each containing 10 hamsters. The group treated with the liposomes of β‐carotene exhibited a significantly lower tumor burden (approx 5,000‐fold difference) than the control tumor group. Electron‐ and light‐micrographic analyses were used to substantiate the g...

Vitamin C enhances the development of carcinomas in the hamster buccal pouch experimental model

Forty young adult male Syrian hamsters (Mesocricetus auratus) were divided into four groups of 10 animals. The animals in group 1 (tumor control) had the right buccal pouches painted three times a week with a 0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil USP with the use of a number 4 sable brush. The animals in group 2 (experimental group) had the right buccal pouches painted with the same solution as group 1. In addition, they received 1 mg ascorbic acid in 0.5 ml mineral oil three times a week on days alternating with the other application. The ascorbic acid was administered by mouth with the use of a pipette. The animals in group 3 received 1 mg ascorbic acid in 0.5 ml mineral oil three times weekly, and the animals in group 4 were untreated controls. The animals were killed after 14 weeks. Tumors were counted and measured. Both right and left (control) pouches were photographed, excised, fixed in formalin, sectioned in paraffin, and studied histologically. The animals that received the ascorbic acid (vitamin C) had significantly larger tumors in the right buccal pouch, although actual numbers of gross tumors were only slightly increased. The figures for tumor burden in the animals in groups 1 and 2 were 364 versus 648 mm3. Histologic study revealed that the animals in group 2 had more anaplastic tumors and a significantly greater number of areas of dysplastic leukoplakia than the animals in group 1.