• 한국환경보건학회지
• /
• 제41권6호
• /
• pp.405-411
• /
• 2015

Objectives: The purpose of this study is to evaluate the optimum conditions for oral mucosal irritation testing using the buccal pouch of hamsters. Methods: Test materials were applied to the buccal pouch of seven-week old male Syrian hamsters (SLC, Japan) four times at one-hour intervals and macroscopic changes were examined at 24 hours after final treatment. After sacrifice, the buccal pouches were removed and prepared for histopathological evaluation. In order to set the exposure time, we performed exposure tests of 5, 12, 18 and 23 minutes using sodium lauryl sulfate (SLS) 1% and set the treatment volume from the test results at 2, 3, or 4 ml treatment using SLS 1%, Triton X-100 1% and ethanol. After setting the experimental conditions, seven groups of materials [sodium lauryl sulfate (SLS) (1%), Triton X-100 (1%), hydrogen peroxide (3%), ethanol (100%), chlorhexidine (0.2%, 2%), phosphate buffer saline (PBS)] were assessed. Results: Experimental conditions of material exposure time were fixed as 18 minutes from the exposure tests of 5, 12, 18 or 23 min using sodium lauryl sulfate (SLS) 1%. Treated volume was set as 4 ml per each pouch from the test results of 2, 3, or 4 ml treatments using SLS 1%, Triton X-100 1% and ethanol. The results in terms of irritation degree were in the order of sodium lauryl sulfate (SLS) (1%) > Triton X-100 (1%) ${\fallingdotseq}$ hydrogen peroxide (3%) > ethanol (100%) ${\fallingdotseq}$ chlorhexidine (0.2%, 2%) > phosphate buffer saline (PBS). Conclusion: From this study, suitable conditions for hamster mucosal irritation testing were suggested and this method was verified through materials commonly used on oral mucosal membranes.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권2호
• /
• pp.951-957
• /
• 2013

Our aim was to investigate the chemopreventive potential of saffron in DMBA-induced hamster buccal pouch carcinogenesis. Assessment was by monitoring the percentage of tumor bearing hamsters, tumor size as well as the status of detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% oral tumor formation with severe histopathological abnormalities in all the hamsters treated with DMBA alone, activities of phase I and phase II detoxification enzymes, lipid peroxidation and antioxidants being significantly altered. Though oral administration of saffron completely prevented the formation of tumors, we noticed severe hyperplasia and dysplasia in hamsters treated with DMBA, suggesting that tumors might eventually develop. Oral administration of saffron return detoxification enzymes, lipid peroxidation and antioxidants to normal ranges. The chemopreventive potential of saffron thus is likely due to antioxidant properties and modulating effects on detoxification in favour of the excretion of carcinogenic metabolites during DMBA-induced hamster buccal pouch carcinogenesis.

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
• /
• pp.118-118
• /
• 2003

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제26권6호
• /
• pp.581-590
• /
• 2000

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Over 30 oncogenes can be activated by insertional mutagenesis, single point mutations, chromosomal translocations and gene amplification. The ras oncogenes have been detected in $15{\sim}20%$ of human tumors that include some of the most common forms of human neoplasia and are known to acquire their transforming properties by single point mutations in two domains of their coding sequences, most commonly in codons 12 and 61. The ras gene family consists of three functional genes, N-ras, K-ras and H-ras which encode highly similar proteins of 188 or 189 amino acid residues generically known as P21. ras proteins have been shown to bind GTP and GTP, and possess intrinsic GTPase activity. Experimental study was performed to observe the mutational change of the ras gene family and apply the results to the clinical activity. 36 Golden Syrian Hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek (control side) was treated with mineral oil as the same manner of the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were completely dissected by microdissection and DNA from both tissue were isolated by proteinase K/phenol/chloroform extraction. Segments of the K-ras and H-ras gene were amplified by PCR using the oligonucleotide primers corresponding to the homologous region (codon 12 and 61) of the hamster gene, and then confirmational change of ras genes was observed by SSCP and autosequencing analysis. The results were as follows : 1. Malignant lesion could be found in the experimental side from the experimental six weeks. 2. One hamster among six showed point mutation of the H-ras codon 12($G{\rightarrow}A$ transition) at the experimental 10 and 14 weeks. 3. One of six at 6 weeks, two of six at 8 weeks and one of six at 12 weeks revealed the confirmational change of the H-ras codon 61($A{\rightarrow}T$ transversion). 4. The incidence of point mutation of H-ras codon 12 and 61 were 5.5%(2 of 36) and 11%(4 of 36) respectively. 5. Point mutation of the K-ras could not be seen during the whole experimental period. Form the above results, these findings strongly support the concept that H-ras oncogenes may have the influence of the DMBA induced carcinoma of hamster buccal pouch.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제31권3호
• /
• pp.219-227
• /
• 2005

Purpose: Abnormalities in the p53 gene are regarded as the most consistent genetic abnormalities detected in head and neck squamous cell carcinogenesis. Two new members of the p53 gene family, p73 and p63 have recently been identified. They share considerable sequence homology with p53 in the transactivation, DNA binding, and oligomerization domains, indicating possible involvement in carcinogenesis. Disruption of the homeostatic balance between proliferation and apoptosis is widely believed to contribute to human oral carcinogenesis. The aim of this study was to analyze expression of p63 in squamous cell carcinogenesis and to compare with immunochemical markers representing cell proliferation and apoptosis. Materials and Methods: Using the Syrian hamster oral cancer model, the fraction of apoptotic (apoptotic index-AI), proliferating (mitotic index-MI) and p63 expressing keratinocytes were examined at normal, dysplastic and malignant oral epithelium using the TUNEL assay, PCNA and p63 immunostaining. Results: p63 significantly increased between normal and dysplastic epithelium and between dysplastic and malignant epithelium. PCNA significantly increased between normal and dysplastic epithelium and between normal and malignant epithelium. However, increase between dysplastic and malignant epithelium, though still increasing, was not statistically significant. The percentage of TUNEL positive cells increased from normal to dysplastic epithelium and returned to normal keratinocyte level in the malignant epithelium. However, differences between tissue types were not significant. The ratio of MI:AI increased significantly only in the dysplastic-malignant epithelial transition. The increase of p63 expression closely reflected the change in the MI:AI ratio during oral carcinogenesis. Conclusion: The p63 may be associated with the regulation of epithelial proliferation and apoptosis in DMBA-induced hamster buccal pouch squamous cell carcinogenesis. Further study is required to investigate which p63 isoforms are involved in hamster buccal pouch carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권7호
• /
• pp.3527-3531
• /
• 2016

Recombinant human bone morphogenetic protein-2 (rhBMP-2 ), a member of the TGF-${\beta}$ family, has been used widely in recent years to regenerate defects of the maxillary and mandible bones. Such defects are sometimes caused by resection of oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP-2 on these carcinomas are not fully clear. The objective of this study was to determine histologically whether rhBMP-2 produces adverse effects on angiogenesis during induction of OSCC, a biologic process critical for tumor formation in an experimental model in the buccal pouch of golden Syrian hamsters. Buccal cavities were exposed to painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, then biopsies were taken. Division was into 2 groups: a study group of 10 hamsters receiving $0.25{\mu}g/ml$ of rhBMP-2 in the $3^{rd}$ and $6^{th}$ weeks; and a control group of 10 hamsters which did not receive any additional treatment. VEGF expression and microvessel density were measured but no differences were noted between the two groups. According to this study, rh-BMP-2 does not stimulate angiogenesis during induction of OCSSs.

• 한국식품과학회지
• /
• 제39권2호
• /
• pp.181-188
• /
• 2007

8주령의 F1B golden Syrian 햄스터에게 동맥경화 유발식이와 함께 녹차 추출물을 각각 500 혹은 1,000 mg/kg b.w.의 양을 매일 경구투여하면서 6주간 사육하였을 때 햄스터 체내의 지질대사와 대동맥 내에서의 지방의 축적 정도에 미치는 영향을 조사하였다. 실험 결과 녹차추출물의 경구투여는 동맥경화유발식이를 섭취하는 햄스터의 혈중 중성지방과 총콜레스테롤치를 농도의존적으로 감소시켰고, 대동맥궁내에서의 지방의 축적을 예방하였다. 특히 녹차추출물 1,000 mg/kg b.w. 투여는 동맥경화유발식이를 섭취한 햄스터에서 간장내의 LDL receptor mRNA level을 증가시키는 경향을 보였다. 이러한 결과로 볼 때 녹차 추출물의 투여는 동맥경화유발식이를 섭취한 햄스터의 혈중 콜레스테롤치를 감소시키고 LDL receptor의 발현을 증가시킴으로써 동맥경화를 예방할 수 있음을 보여주었다.

• Parasites, Hosts and Diseases
• /
• 제51권6호
• /
• pp.711-717
• /
• 2013

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제27권2호
• /
• pp.135-141
• /
• 2001

Recently, the consumption of soy products has been associated with low rates of hormone-dependent and hormone-independent cancers. Asians, who consume $20{\sim}50times$ more soy per capita than Americans, have lower incidence and death rates from breast and prostate cancer. Because soy contains the isoflavones genistein and daidzein (present as their glycosidic conjugates) at mg/g concentrations, it has been suggested that isoflavones might be acting as natural chemopreventive agents. During the 1980s several groups of investigators carried out experiments to test the effectiveness of soy in the diet in animal models of cancer. These studies reported a protective effect of soy; none showed that soy increased cancer risk. Genistein was shown to inhibit the growth of a wide variety of tumor cell types in culture. The purpose of this study was to evaluate the effects of genistein on the carcinogenesis induced by topical application of 0.5% 9, 10-dimethyl 1,2-benzanthracene (DMBA) on the hamster buccal pouch. 48 syrian hamsters were employed in this study, divided into experimental group and control. 24 animals (DMBA topical application group) had the right buccal pouch painted 3times weekly with 0.5% DMBA in mineral oil, 24 animals (genistein group) were supplied with 0.1mg genistein with DMBA topical application. 3 animals in the experimental group and control were sacrificed at serially each other week after experiments. Their buccal pouches were removed and routinely processed for microscopic examination. The results were as follows: 1. In DMBA topical application and genistein group, they showed carcinogenesis as time goes by experimental stage. 2. Genistein group was retarded in carcinogenesis related to the acanthosis, hyperkeratosis, epithelial dysplasia. 3. p53 immunohistochemical study showed that the p53 protein of genistein group was less expressed than that of the control group. Thus, it seems that genistein has chemopreventive effect on the carcinogenesis in the oral cavity, but further study is required to elucidate the anticancer mechanism of genistein.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제30권5호
• /
• pp.400-405
• /
• 2004

Angiogenesis inhibition is major concern to cancer chemotherapy and many studies about compound inhibiting angiogenesis is in progression. The long-known preventive effect of plant-based diet on tumorigenesis and other chronic diseases is well documented. Especially soy extract, genistein, is known to be potent angiogenesis inhibitor and prevent development and progression of tumor. In the present study, the effect of angiogenesis on tumorigenesis and chemopreventive effect of genistein by angiogenesis inhibition in hamster buccal pouch oral carcinigenesis model induced by 7.12-dimethylbenza(a)nthracene (DMBA) was studied. Forty eight Syrian Golden young adult hamsters (150-200 gm) were divided into two groups. In control group, 0.5% DMBA in heavy mineral oil was applied to hamster buccal pouch three times a week and in experimental group, 0.1 mg of genistein is administered orally everyday in addition to DMBA application. The animals were euthanized from 2 weeks to 16 weeks with interval of 2 week. H&E staining and immunohistochemistry was performed to evaluate microvessel density by using factor VIII-related antigen and avidin-biotin technique. Microvessels per area was quantified and compared between control and experimental group statistically. The results were as follows. 1. Microvessel density was increased time dependently in both groups and especially the increase was significant from 12 weeks to 16 weeks. 2. When comparing both group, the experimental group showed significantly low microvessel density than control group in 12 weeks (p=0.043), 14 weeks (p=0.050), 16 weeks (p=0.037). Based on these results, it was concluded that genistein influenced oral carcinogenesis by angiogenesis inhibition.