Protective Effect of White-fleshed Peach (Prunus persica (L.) Batsch) on Chronic Nicotine-induced Toxicity

BACKGROUND: Nicotine is a major toxic component of tobacco smoke and has been recognized as a risk factor to induce oxidative tissue damage, which is a precursor to cardiovascular diseases, lung-related diseases, and cancers. Peaches (Prunus persica) have been used for the treatment of degenerative disorders, such as hypermenorrhea, dysmenorrhea, and infertility in Asian countries. In this study, we investigated the effects of white-fleshed peach on the excretion of nicotine metabolites and 1-hydroxypyrene in smokers and chronic nicotine-induced tissue damages in mice. METHODS: The concentrations of cotinine and 1-hydroxypyrene were measured in urine of smokers before or after intake of white-fleshed peaches. In addition, ICR mice were injected with nicotine (5 mg/kg body weight) and then orally administered with white-fleshed peach extracts (WFPE) (250 or 500 mg/kg body weight) for 36 days. The oxidative stress parameters and the activities of antioxidant enzymes were measured in liver and kidney tissues. Also, histological changes and nitrotyrosine expression were assessed. RESULTS: Intake of white-fleshed peaches increased the urinary concentration of nicotine metabolites and 1-hydroxypyrene in 91.67% and 83.33% of smokers, respectively. WFPE decreased the malondialdehyde levels and recovered the activities of antioxidant enzymes in nicotine-injected mice. In addition, WFPE inhibited nitrotyrosine expression and inflammatory responses in the liver, kidney, and lung tissues of nicotine-treated mice. CONCLUSIONS: White-fleshed peaches may increase the metabolism of toxic components in tobacco smoke in smokers and protect normal tissues against nicotine toxicity in mice. Therefore, supplementation of white-fleshed peaches might be beneficial to smokers.

The Inhibitory Effects of Forsythia Koreana Extracts on the Metastatic Ability of Breast Cancer Cells and Bone Resorption by Osteoclasts

BACKGROUND: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. METHODS: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. RESULTS: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor β1-induced migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. CONCLUSIONS: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

Validating of the pre-clinical mouse model for metastatic breast cancer to the mandible

Metastatic breast carcinoma has a great tendency to spread to the mandible. It is concomitantly associated with bone destruction, food intake disorder, and a poorer prognosis. Appropriate animal models need to be developed for a better understanding of the mechanisms underlying the metastatic process of breast cancer cells to mandible and to test the effects of potential lead compounds. Here, we assessed the metastasis model of intracardiac injection using luciferase-transfected metastatic breast cancer cells (MDA-MB-231Luc+) by determining the incidences of metastasis, mCT images, and histopathological results. A high bioluminescence signal mainly detected mandibular lesions with less frequent distal femora and proximal tibiae lesions. Extensive mandibular bone destruction occurred in nude mice grafted with metastatic breast cancer cells. This type of animal model might be a useful tool in assessing therapeutic implications and the efficacy of anti-cancer drugs for osteolytic cancers.

Isoliquiritigenin Inhibits Metastatic Breast Cancer Cell-induced Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin Ratio in Human Osteoblastic Cells

Bone destruction induced by the metastasis of breast cancer cells is a frequent complication that is caused by the interaction between cancer cells and bone cells. Receptor activator of nuclear factor kappa-B ligand (RANKL) and the endogenous soluble RANKL inhibitor, osteoprotegerin (OPG), directly play critical roles in the differentiation, activity, and survival of osteoclasts. In patients with bone metastases, osteoclastic bone resorption promotes the majority of skeletal-related events and propagates bone metastases. Therefore, blocking osteoclast activity and differentiation via RANKL inhibition can be a promising therapeutic approach for cancer-associated bone diseases. We investigated the potential of isoliquiritigenin (ISL), which has anti-proliferative, anti-angiogenic, and anti-invasive effects, as a preventive and therapeutic agent for breast cancer cell-induced bone destruction. ISL at non-toxicity concentrations significantly inhibited the RANKL/OPG ratio by reducing the production of RANKL and restoring OPG production to control levels in hFOB1.19 cells stimulated with conditioned medium (CM) of MDA-MB-231 cells. In addition, ISL reduced the expression of cyclooxygenase-2 in hFOB1.19 cells stimulated by CM of MDA-MB-231 cells. Therefore, ISL may have inhibitory potential on breast cancer-induced bone destruction.

Polymorphisms of CYP1A1 and GSTM1 Genes and Susceptibility to Oral Cancer

PURPOSE: Oral cancer is the fifth most common form of cancer in the world and comprises 6.5% of all cancer deaths. Since one of the major risk factors for oral cancer is tobacco use, we hypothesized that polymorphic genes coding for tobacco carcinogen-metabolizing enzymes may play a role in oral cancer susceptibility. MATERIALS AND METHODS: To investigate the association between polymorphisms of the CYP1A1 and GSTM1 genes and risks for oral squamous cell carcinoma (OSCC) in the Korean population, the prevalence of the CYP1A1 Mspl and GSTM1 null polymorphisms were examined in 72 patients with histologically confirmed primary OSCC, as well as in 221 healthy control subjects. RESULTS: A significant risk increase for oral cancer was observed among subjects with the homozygous CYP1A1 (m2/m2) genotype (OR=3.8, 95% CI=1.9-7.7), but not the GSTM1 null genotype (OR=0.7, 95% CI=0.4-1.3). Risk for oral cancer was significantly increased in subjects with the homozygous CYP1A1 (m2/m2)genotype, regardless of smoking history (smokers; OR=4.4; 95% CI=1.2-16.3; non- smokers OR=4.9; 95% CI=1.9-12.5). Using the potentially most protective genotype GSTM1 (+)/CYP1A1 [(m1/m1)+ (m1/m2)]as the reference group, an increased risk for oral cancer was observed among subjects with the GSTM1 (+)/ CYP1A1 (m2/m2) (OR= 2.0, 95% CI=0.8-5.2), and GSTM1 (-)/ CYP1A1 (m2/m2) (OR=4.9, 95% CI=1.5-15.5) genotypes (p < 0.009, (chi-square trend test). CONCLUSION: Our results suggest that individuals with a genotype of CYP1A1 (m2/m2) and GSTM1(-) are highly susceptible for OSCC and that the CYP1A1 (m2/m2) genotype is closely associated with increased risk of OSCC in Koreans.

Inhibition of Phorbol Ester-induced Mouse Skin Tumor Promotion and COX-2 Expression by Celecoxib: C/EBP as a Potential Molecular Target / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Inflammation acts as a driving force for the development of cancer. Multiple lines of evidence suggest that nonsteroidal anti-inflammatory drugs, especially those that specifically target cyclooxygenase-2 (COX-2), are effective in preventing certain cancers. The present study was aimed at investigating the antitumor promoting potential of celecoxib in chemically induced mouse skin tumorigenesis, as well as elucidating the underlying molecular mechanisms. MATERIALS AND METHODS: To study the antitumor promoting effects of celecoxib, we used the classical two-stage mouse skin tumorigenesis model that involves initiation with a single application of 7,12-dimethylbenz[alpha]anthracene (DMBA) followed by promotion with repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of celecoxib on the expression of COX-2, vascular endothelial growth factor (VEGF), p65 and the different isoforms of CCAAT/enhancer binding protein (C/EBP) were examined by performing Western blot analysis. Electrophoretic mobility gel shift assay was used to examine the effects of celecoxib on the TPA-induced DNA binding activities of various transcription factors. RESULTS: Our study revealed that topical application of celecoxib (10 micromol) significantly reduced the multiplicity of papillomas in DMBA-initiated and TPA-promoted mouse skin. Pretreatment with celecoxib also diminished the expression of COX-2 and VEGF in the mouse skin papillomas. Pretreatment with celecoxib attenuated DNA binding of transcription factor (C/EBP) in the TPA-stimulated mouse skin. Moreover, celecoxib suppressed the TPA-induced nuclear expression of C/EBPdelta, but not C/EBPbeta, in mouse skin in vivo. CONCLUSION: Our study demonstrates the inhibitory effects of celecoxib on mouse skin tumor promotion, which was associated with a decreased expression of COX-2 and VEGF, as well as inhibition of C/EBP activation.

Generation of a transgenic mouse model to study cranial suture development; Apert syndrome / 대한치과교정학회지

The form and function of the craniofacial structure critically depend on genetic information. With recent advances in the molecular technology, genes that are important for normal growth and morphogenesis of the craniofacial skeleton are being rapidly uncovered, shaping up modern craniofacial biology. One of them is fibroblast growth factor receptor 2 (FGFR2). Specific point mutations in the FGFR2 gene have been linked to Apert syndrome, which is characterized by premature closure of cranial sutures and craniofacial anomalies as well as limb deformities. To study pathogenic mechanisms underlying craniosynostosis phenotype of Apert syndrome, we used a transgenic approach; an FGFR2 minigene construct containing an Apert mutation (a point mutation that substitute proline at the position 253 to arginine; P253R) was introduced into fertilized mouse germ cells by DNA microinjection. The injected cells were then allowed to develop into transgenic mice. We used a bone-specific promoter (a DNA fragment from the type I collagen gene) to confine the expression of mutant FGFR2 gene to the bone tissue, and asked whether expression of mutant FGFR2 in bone is sufficient to cause the craniosynostosis phenotype in mice. Initial characterization of these mice shows prematurely closed cranial sutures with facial deformities expected from Apert patients. We also demonstrate that the transgene produces mutant FGFR2 protein with increased functional activities. Having this useful mouse model, we now can ask questions regarding the role of FGFR2 in normal and abnormal development of cranial bones and sutures.

Expression of matrix metalloproteinase-1 and -2 mRNA in retrodiscal tissue of the temporomandibular joint

Matrix metalloproteinases (MMPs) play an important role in the normal morphogenesis, maintenance, and repair of matrix and also have important functions in pathologic conditions characterized by excessive degradation of extracellular matrix, such as rheumatoid arthritis, osteoarthritis, periodontitis and in tumor invasion and metastasis. In this study, expression of MMP-1 and -2 mRNA in retrodiscal tissue of the temporomandibular joint (TMJ) was examined and compared with magnetic resonance imaging (MRI) and surgical findings. MMP mRNAs in the retrodiscal tissue samples were detected by reverse transcription - polymerase chain reaction. TMJ internal derangement (ID) was categorized as normal disc position, disc displacement with reduction, early stage of disc displacement without reduction (DDsR) and late stage of DDsR. TMJ osteoarthrosis (OA) was classified with normal, mild and advanced OA. The amount of synovial fluid collection was divided into not detected, small, large and extremely large amount on MR T2-weighted imaging. Perforation and adhesion were examined during open surgery of the TMJ. Six out of 37 samples were excluded because of little amount of extracted total mRNA. MMP-2 mRNA was detected whole joints, and so the MMP-2 mRNA seems to be expressed normally in retrodiscal tissue. However, MMP-1 mRNA was expressed in 8 of 31 joints. Frequencies of MMP-1 mRNA expression according to the TMJ IDs, amount of synovial fluid and surgical findings made no significant difference. MMP-1 mRNA was detected more frequently in OA groups (7/16 joints, 43.8%) than in normal bony structure group (1/15,joints, 6.7%). Expression of MMP-1 mRNA in retrodiscal tissue might be related with OA of the TMJ.

The Effect of Azithromycin on the Cyclosporin- Ainduced Gingival Fibroblast Overgrowth / 대한치주과학회지

No abstract available.

A Study on the Validity of College of Dentistry Transfer System / 한국의학교육

The purpose of this study is to examine the validity of the College of Dentistry transfer system. The study focused on the correlation between entree examination results and class achievement of transfer students and double major students, grades difference according to school year and their major of previous schools. Also, there was the comparison of school life satisfaction among the transfer students, double major students and ordinary students of dentistry school. The result of the research is as follows; First, there was no significant relation between the entree examination results and class achievement of transfer students and double major students, suggesting the entree examination results cannot be a reasonable prediction for class achievements. Second, there was no significant difference in the grades according to school year and their major of previous schools, showing that students can well adjust themselves no matter what their majors are. Third, there was a significant difference in transfer and double major students' grades, and showed higher achievement as their school year passed. Fourth, the transfer and double major students were more satisfied in school life than the ordianry students. On the basis of the above findings we can conclude the transfer student system of college of dentistry was successful, but needs some improvements in such as student selection, welfare facilities and school culture.

Genetic polymorphisms of the glutathione s-transferase and cyp1a1 genes in korean oral squamous cell carcinoma

Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the poly-morphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymor-phisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozy-gote( m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic poly-morphisms exist among different ethnic group and different types of human cancer.

Sequence Analysis of ABO Gene in Korean for Individual Identification / 대한법의학회지

This study intends to evaluate usefulness of ABO gene in forensic identification. The genotype and allele frequency of ABO gene was investigated and the power of identification information of ABO gene was calculated. 100 unrelated Korean individuals were selected. DNA was extracted from sample and PCR and sequencing were performed to analyze sequence of exon 6 and exon 7 in ABO gene, the following results were obtained: 1. The polymorphic nucleotide positions of ABO gene are 216, 297 in exon 6 (2 positions) and 467, 526, 579, 646, 657, 681, 703, 771, 796, 803, 829, 930 in exon 7 (12 positions) in Korean. 2. Amomg Korean population, 18 ABO genotypes and 7 alleles were observed. O01 is most frequent (27.6%) and then A102 (22.0%), B101 (22.0%), O02 (21.0%). 3. In A type allele, the frequencies of A101 and A102 are 21.4%, 78.6% respectively. And in B type, B101 is 97.7%, the most part of them. In O type, O01 is 56.0%, O02 is 42.0% and O04 is 2.0%. 4. The observed heterozygosity and the expected heterozygosity is 0.670, 0.784 each. The polymorphism information content (PIC) is 0.744. The power of discrimination (PD) and the mean exclusion chance (MEC) are calculated to be 0.924 and 0.576. Based on the results of this study, the determination of ABO genotype by sequencing may be useful in forensic identification including finding an individual in relation to criminal case, paternity test, and confirming possible relationships between family members.

Sex Differences in the Mandibular Rami of Korean Adults: Radiographic Study / 체질인류학회지

Mandibles and crania were measured with anthrophological methods on cephalometric radiogrphs of 241 Korean adults. It was tried to identify sex differences with a special attention to the mandibular flexure. The relationships between mandibular flexure and mandibular growth pattern, antegonial notch, and gonial angle were investigated. Most of measurements except gonial angle were larger in male than in female. However, the cranial base angle was larger in female than in male and the height of mandibular flexure was higher in female. Mandibular flexure tends to be deeper when gonial angle is small, mandibular ramus is long, and antegonial notch is deep. Mandibular body length becomes larger when SNB becomes larger. As mandibular plane angle becomes larger, so cranial base angle and gonial angle become larger and as mandibular plane angle does, so maximum cranial height and SNB become smaller. In conclusion, sex difference of mandibular flexure is important, however, sex determination accuracy using mandibular flexure is not accurate as previously reported.

Non-metric Traits of Korean Mandibles / 체질인류학회지

Mandible is the biggest and the hardest facial bone and its shape is found well-remained in the fossil and forensic research area. Therefore it is of significance in physical anthropology and it has been used to distinguish the different ethnic groups as well as the sex. The researchers took 102 mandibles in Korean of the known sex and examined the physical anthropologic characteristics that exist among the Korean males and females as well as the different ethnic groups. Through examining 13 criteria that include the shape of the chin and the shape of mental spine the following results were achieved. Out of the 13 non-metric criteria of the examined mandibles, Concerning the sexual dimorphism, the most distinguished criteria was the contour of the mandibular lower border. In males, 68.1% showed the "rocker form", on the other hand in females, the "straight form" was more general (82.0%). In addition, the shape also differed in mental region. In males the shape of the chin was bilobate or square form generally (91.7%), while females' mandible wasn't bilobate form, but square (53.6%) and pointed form (46.4%). Beside this, there was no differences between the male and female. We compared in presence of mylohyoid canal in Korean with the other ethnic groups by non-metric traits. The mylohyoid canal was relatively low by 5% among the Asians including the Koreans and relatively high by 10.0% among the Whites and over 15.0% among the Blacks.

Cloning and Sequence Analysis of Gene Encoding an Outer Membrane Protein ( OmpTL ) of Treponema Strain PFB4G Isolated from Periodontitis Patients

Treponema strain PFB4G is a novel oral spirochete and one of the most frequently detected organisms in subgingival plaque samples from rapidly progressive periodontitis and adult periodontitis patients. In this study, a genomic library of Treponema strain PFB4G was constructed in lambdaZAP expression vector. One positive clone that carried a 2.6-kb fragment was identified by screening with chicken Ig Y (immunoglobulin yolk) antibody raised against whole bacterial sonicates. Nucleotide sequencing of the subclones revealed an open reading frame (ORF) lacking the 5'-end. This region was obtained by PCR amplification using a degenerative and a specific primer. A complete open reading frame of 1,770 bp was identified and the deduced polypeptide consisted of 590 amino acids with a molecular mass of 65 kDa. The polypeptide, designated as OmpTL, had a typical prokaryotic signal sequence (19 amino acids) with a potential cleavage site for signal peptidase I and showed a significant level of homology with the outer membrane proteins of other oral treponemes, especially with that of Treponema maltophilum. The isolation of the gene encoding an outer membrane protein may allow the study of their roles in future, possibly as adhesion, pore forming or induction of proinflammatory cytokine synthesis.

The Effects of Nicotine and NNK on gingival fibroblast / 대한치주과학회지

In order to observe the effects of Nicotine and NNK on cultured human gingival fibroblast, several factors were examined including mutagenicity, the number of cells attached culture plate surface through MTT test, the abundance of collagen & collagenase in mRNA level and collagenolytic activity in extracellular matrix. The results were as follows; 1. Regardless of the co-existence of S9, Nicotine did not show the mutagenicity by itself and NNK by itself showd the same result; However, dose related mutagenicity was shown in NNK with S9. 2. The number of fibroblasts attached cultured plate surface was measured by MTT procedure. The number of cells in Non-smokers increased at all time periods as compared to those of smoker. 3. Non-smoker's fibroblast treated by NNK or Nicotine was dose-dependently decreased in the number of cells when compared to untreated control. In higher dose, Nicotine showed the cellular toxicity , but NNK did not. 4. No change in the abundance of mRNA for proalpha1 and proalpha2 was shown in Nicotine treated group but in gingival fibroblasts following treatment with NNK, the abundance of mRNA for proalpha1, but not proalpha2 collagen was decreased. 5. The abundance of mRNA for collagenase was decreased when NNK was treated but no change occurred in Nicotine treated group. 6. The effect of NNK and Nicotine in collagenolytic activity showed that ,collagenase activity exclusively react to type I collagen, was increased in both group, but gelatinase exclusively react to type IV collagen was not influenced at all. Collagenase activity of smoker's fibroblast was also increased as much as Nicotine and NNK group. The findings suggest that both of Nicotine and NNK lead gingival fibroblast to decrease in the abundance of collagen. And it seems to be that Nicotine and NNK have independent pathway toward the gingival fibroblast.

Slow-release local drug delivery effect of tetracycline loaded calcium sulfate / 대한치주과학회지

Periodontal disease is a bacterially caused by disease. To remove plaque and bacteria, it has been necessary to prescribe chemical drug to patient to subjugate therapeutic unvalue by mechanical scaling. As a patient on a high dosage of the antibiotics to maintain the effective concentration may produce unfavorable side effects, this decase demands the Slow-release local drug delivery system. The object of the experiment is to study on the slow-release local drug delivery effects of calcium sulfate compounded with tetracycline that mainly used in periodontal disease. Experimental groups were divided into four classes as follow: Group 1 : 10% tetracycline compounded modified calcium sulfate paste. Group 2 : compounded and hardened 10% tetracycline and calcium sulfate. Group 3 : compounded 10% tetracycline and calcium sulfate, used just before hardened. Group 4 : tetracycline-ethylene vinyl acetate fiber. In the four groups, release concentration, it's durability and the period of absorption by times are observed and concluded as follow: 1. An effective concentration(4microgram/ml) remained until 5 weeks in group 1, 9 days in group 2, 7 days in group 3, 15 days in group 4. 2. It was fully fused at 11.8 days average in group 2 and 14.8 days average in group 3. 3. There were no statistically significant results in tetracycline concentration until a week in group 2 and 3(p<0.05) These results suggest that tetracycline loaded calcium sulfate release sufficient tetracycline and fused in 11~14 days, so calcium sulfate is useful carrier as slow release local drug delivery system

The Histologic Study of Skin Tumors Induced by Ethyl Carbamate and Its Metabolites / 대한피부과학회지

BACKGROUND: Ethyl crbmate(EC) has been identified at low microgram quantities in various fermented beverages, destiled products and tobacco smoke. EC has long been known as a carcinogen. Oxidation of the ethyl group of EC is followed by dehydration to yield the carcinogen vinyl carbamate (VC). This is further oxidized to vinyl carbamate epoxide(VCO). VC and VCO proved to be much more carcirogenic than EC. OBJECT: The objective of this study is to compare the potency of carcinogenic ability and histologic changes in skin tumors induced by EC, VC, or VCO. METHODS: In this exeriment, the tumor induction was performed by painting the mouse skin once a week for five weeks with EC, VC and VCO solution, and then 12-0-tetradecanoyl-phorbol-13-acetate(TP2) was treated in the same manner twice a week for 35 weeks. We biopsied the skin at B 0, 15, 25, 30 and 35 weeks and stained the specimens with hematoxylineosin. RESULTS: The time period for the first appearance of papilloma was 6 weeks in the VC-TPA and VCO-TPA group, but, 15 weeks in the EC TPA group. The average number of papilloma showed a statistically sign.ficant difference after 15 weeks between the EC-TPA, VC-TPA and VCO-TPA group. The occurrence of keratoacanthoma and squamous cell carcinoma was 16 and 21 weeks respectively. Histologic changes, such as epidermal layers, pseudohorncysts, degree of hyperkeratosis, hypergranulosis, dysplasia and dyskeratotic cells were more prominent in the papil loma than in the non-papilloma lesion. Dermal changes disclosed similiar findings, that is, increased dermal thicknes, proliferation of vessels and hair follicles, and fibrosis of the dermis. Squamous cell carcinomis and keratoacanthomas were produced only in the VCO-TPA group. CONCLUSION: From the above results it is concluded that VC and VCO have a more potent carcinogenic potential than EC. Various skin tumors, such as papilloma, keratoacanthoma or squamous cell carcinoma were prorduced by the above carcinogens.

Tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenzaanthracene

The incidence of tumor and the time of expression, cellular localization and the molecular weight of tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) with or without 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were studied. The time of the development of skin tumors in 0.1% DMBA-TPA treated rats was significantly shorter than that in rats which were treated with DMBA alone. In the complete carcinogenesis case, papillomas developed more slowly and were less common and also squamous cell carcinomas appeared much later. From the analysis of the proteins of each experimental group by SDS-PAGE and two dimensional gel electrophoresis, at least three tumor associated proteins were identified (54kd, pl = 5.66; 27kd, pl = 5.85; 11kd, pl = 4.90). Also these proteins were found in rat dorsal skin from 14 days gestation to 21 days postpartum, and disappeared after 28 days. In conclusions, two stage skin carcinogenesis could be successfully demonstrated in Sprague-Dawley rats and abnormal proteins were produced in DMBA or DMBA-TPA induced skin tumor. The tumor associated proteins of skin tumor induced by DMBA or DMBA-TPA were appeared at the late initiation stage or early promotion stage, and they were localized in plasma membrane and were glycoproteins that are thought to be related to the epidermal differentiation process.

Tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenzaanthracene

The incidence of tumor and the time of expression, cellular localization and the molecular weight of tumor associated proteins of rat skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) with or without 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were studied. The time of the development of skin tumors in 0.1% DMBA-TPA treated rats was significantly shorter than that in rats which were treated with DMBA alone. In the complete carcinogenesis case, papillomas developed more slowly and were less common and also squamous cell carcinomas appeared much later. From the analysis of the proteins of each experimental group by SDS-PAGE and two dimensional gel electrophoresis, at least three tumor associated proteins were identified (54kd, pl = 5.66; 27kd, pl = 5.85; 11kd, pl = 4.90). Also these proteins were found in rat dorsal skin from 14 days gestation to 21 days postpartum, and disappeared after 28 days. In conclusions, two stage skin carcinogenesis could be successfully demonstrated in Sprague-Dawley rats and abnormal proteins were produced in DMBA or DMBA-TPA induced skin tumor. The tumor associated proteins of skin tumor induced by DMBA or DMBA-TPA were appeared at the late initiation stage or early promotion stage, and they were localized in plasma membrane and were glycoproteins that are thought to be related to the epidermal differentiation process.