There exists a profound need for biomarkers that will allow for better screening and risk stratification for colorectal cancer (CRC). With the advent of the newly termed "metabolic syndrome", CRC prevalence is trending upwards even with much improved screening protocols and remains the second leading cause of cancer related morbidity. The "metabolic syndrome" refers to a range of environmental risk factors, including diabetes and obesity, thought to be increasing the prevalence of CRC. An altered metabolism is seen in metabolic syndrome, which affects cancer through changes in the relationship between glycolysis, the Krebs cycle, and mitochondrial oxidative phosphorylation (OXPHOS). Specifically, it has been observed that highly proliferative tumorigenic cells are undergoing a shift away from the energy efficient OXPHOS and toward aerobic glycolysis even under normoxic conditions. This effect has been termed, the Warburg Effect. As a consequence of endogenous (e.g. genetic, diabetes etc.) and exogenous (e.g. diet, smoking etc.) factors, alterations in cell proliferation/death have been shown to occur throughout the colon reflecting the diffuse "field of injury" (field carcinogenesis). Also due to high energy demands it is recognized that the hyper-proliferative mucosa contiguous to colonic tumors may be hyper-metabolic. Our group has been interested in elucidating the biological nature of field carcinogenesis and assesses expression of key metabolic markers in the rectal biopsies from patients who harbor neoplasia elsewhere in their colon. We found key indications of a glycolytic shift toward aerobic glycolysis with upregulation of glucose transporter (GLUT1) as well as pyruvate shunting away from OXPHOS via pyruvate kinase muscle 2 (PKM2). These changes were further corroborated by an increase in hypoxia inducible factor 1 alpha (HIF1alpha), which is normally seen to increase glycolytic function in hypoxic conditions. Along with these glycolytic changes we also found mitochondrial dysfunction in patients with adenomas. Specifically, mitochondrial mass was found to be increased, with increases in mtDNA as well as upregulation of mitochondrial fusion via optic atrophy 1 (OPA1). Uncoupling protein 2, which decouples OXPHOS from ATP synthesis in the mitochondria, was also found to be upregulated. These findings represent a novel panel of biomarkers for assessing CRC risk via analysis of metabolic dysfunction in the easily accessible rectal epithelium.

The human thyroid epithelial cell HTori-3 has been transformed with doses of either chronic and acute x-rays or strontium beta particles. Models of the past have relied upon animal cell systems to mimic in vitro carcinogenesis. The HTori-3 system hoped to overcome the limitations associated with these types of models by using a human thyroid cell line immortalised with the SV40 virus. HTori-3 human thyroid epithelial cells were irradiated in vitro, passaged and then transplanted into nude mice. Tumours that grew over a 2-6 month period were excised and re-established in culture. Samples were stored and all tumours were taken for histological examination. Chromosome spreads confirmed the human nature of all tumours. Following exposure to acute x-rays in the range of 0.25-2.0 Gy 13 tumours were observed in 25 recipients. Following 0.25-2.0 Gy of chronic x-rays 10 tumours from 25 recipients were observed. From a single 2 Gy exposure of strontium beta particles 3 primary tumours from 5 recipients were observed. The largest of these was re-transplanted in nude mice resulting in 100% incidence. All tumours were classified as undifferentiated anaplastic carcinomas. A small number of tumours were observed in the control cell lines, these may be the result of a general instability found with the partial transformed parental cell line. All 2Gy tumours and those previously established from this laboratory after alpha or gamma radiation were used to test for the presence of the delayed lethal death phenotype. A number of cell and molecular endpoints were used. These included plating efficiency, cell adherence, micronucleus formation and p53 status. In all incidences, the reproductive viability of irradiated cells was below that of non- irradiated cells at up to 4 weeks post-irradiation. The HTori-3 cell line and the techniques used to study the delayed effects of radiation may be applicable to other cell systems and may be a useful model to study the long-term effects of radiation induced genomic instability.

Made available in DSpace on 2014-06-11T19:31:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-29Bitstream added on 2014-06-13T19:20:20Z : No. of bitstreams: 1 andrade_fhe_dr_botfmvz.pdf: 2356107 bytes, checksum: d19c5a3663413870e6a4b3b5625849d2 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Cromatografia Líquida de Alta Eficiência – HPLC foi adaptada para detectar e identificar inseticidas piretróides no tecido adiposo adjacente ao tumor maligno de mama de 10 cadelas, sem predileção por raça e idade. Após a cirurgia, as massas eram examinadas cuidadosamente para lesões neoplásicas malignas. Cinco gramas de tecido adiposo adjacente ao tumor foram colhidos para demonstração de contaminantes ambientais. Os piretróides identificados foram aletrina, cialotrina, cipermetrina, deltametrina e tetrametrina, com nível de contaminação de 40%. A histopatologia demonstrou sete cadelas (70%) como carcinoma complexo, duas (20%) com carcinoma simples e uma (10%) com carcinoma anaplásico. Desses tumores, (80%) apresentaram grau III e (20%) grau I de agressividade. O nível de contaminação foi observado nos tumores mais agressivos. Esta foi à primeira demonstração que se tem conhecimento que o nível de contaminates ambientais pode ser detectado no tecido adiposo de cadela com tumor maligno de mama, pela HPLC. O presente resultado sugere que contaminantes ambientais possam estar envolvidos com o processo de formação ou associação ao risco de desenvolvimento do câncer de mama de cadela, sendo um indicador para auxiliar na monitoração de piretróides. / High Precision Liquid Chromatography – HPLC was adapted to detect and identify pyrethroid insecticides in adipose tissue adjacent to malignant tumor mammary gland tumor in 10 female dogs, without predilection for breed or age. After surgery, the masses were examined carefully for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected for demonstration of environmental contaminants. The pyrethroids identified were allethrin, cyalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 40%. The histopathology demonstrated seven female dogs (70%) as having complex carcinoma, two (20%) with simple carcinoma and one (10%) with anaplastic carcinoma. Of these tumors, (80%) presented aggressiveness degree III and (20%) degree I. The contamination level was observed in more aggressive tumors. This was the first known demonstration in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. The present result suggests that environmental pollutants can be involved with the formation process or association to the risk of development of female dog's breast cancer, being an indicator to aid in monitoring pyrethroids.

Made available in DSpace on 2014-06-11T19:33:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-06-10Bitstream added on 2014-06-13T21:06:01Z : No. of bitstreams: 1 mainenti_p_dr_sjc.pdf: 825103 bytes, checksum: cb4ac2ce4ddd387d52a086efa8ec1795 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A carcinogênese química em glândulas salivares animais não se apresenta como um modelo novo de pesquisa. O uso de DMBA em glândulas submandibulares de ratos produz carcinomas e sarcomas, associados ou não. Apesar de bem estudada a histopatologia deste tipo de carcinogênese, pouco se sabe em relação a imunoistoquímica das neoplasias. Este estudo se propõe a revisar pesquisa pregressa realizada por Mainenti (2006), na tentativa de melhor entender a formação de tumores induzidos por DMBA. O estudo original diagnosticou lesões não neoplásicas, principalmente sialadenites, e tumores como carcinomas, carcinossarcomas e um caso de sarcoma. O presente trabalho fez uso de lâminas e material de estoque em formol. Foram comparadas as lâminas originais com novas lâminas coradas em hematoxilina e eosina. Para a pesquisa de fibras colágenas utilizou-se a coloração pelo método do tricrômico de Gomori. A imunoistoquímica foi realizada utilizando os seguintes anticorpos: AE1/AE3, vimentina, α-SMA, calponina, desmina, miogenina, S-100, CerbB-2 e EMA. Certas lesões, previamente diagnosticadas como sialadenites, foram reclassificadas como carcinomas. A imunoistoquímica foi positiva para os seguintes anticorpos: AE1/AE3 para neoplasia epitelial, vimentina para tecido conjuntivo e tumores mesenquimais, α-SMA e calponina para poucas células fusiformes pleomórficas no estroma dos carcinomas e nas neoplasias mesenquimais. Concluiu-se que a imunoistoquímica revelou diferenciação muito sugestiva de miofibroblastos no estroma dos carcinomas e miofibroblastos compondo o fibrossarcoma e os carcinosarcomas. Estas células produziram colágeno revelado pelo tricrômico de Gomori. O componente epitelial neoplásico foi sugerido como derivado de células luminais. / The chemical carcinogenesis, addressed to animal salivary gland, is not a novel research. The use of DMBA in rat’s submandibular salivary gland is known to produce neoplasms like sarcomas and carcinomas either intermingled or not. Despite of the good amount of information regarding DMBA carcinogenesis histopathology in rat’s submandibular parenchyma, little is known about the immunohistochemistry in such tumors. We proposed a revision of a previous research conduced by Mainenti (2006), in attempt to better understand the neoplasm formation after DMBA. The original experiment disclosed non neoplastic lesions, mainly sialadenitis, and tumors like carcinomas, carcinosarcomas and one case of sarcoma. The present work used all the material from the first research like surgical specimens in formol and slides. We compared the previous hematoxylin and eosin slides with new ones. We also used Gomori’s trichrome in order to disclose collagen fibers. The immunohistochemistry was performed using the following antibodies: AE1/AE3, vimentin, α-SMA, calponin, desmin, myogenin, S-100, CerbB-2 and EMA. Some previous lesions, presented as benign ones, were diagnosed as carcinomas. The immunohistochemistry was positive as shown: AE1/AE3 for epithelial neoplasm, vimentin for connective tissue in mesenchymal tumors, α-SMA and calponin for scarce pleomorphic fusiform cells in the stroma of the carcinomas and in the mesenchymal neoplasms. We concluded that the immunohistochemistry strongly suggested myofibroblast differentiation in the stroma of the carcinomas and myofibroblast cells related to the fibrosarcoma and carcinosarcomas. These cells produced collagen shown after Gomori’s trichrome. The epithelial neoplasm component was suggested as derived from luminal cells.

Made available in DSpace on 2014-06-11T19:33:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T21:06:02Z : No. of bitstreams: 1 grassi_tf_dr_botfm.pdf: 2406422 bytes, checksum: 14575fe8c9692ee11119e80270b7322f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Not available.

Resumo: A survivina é uma proteína inibidora da apoptose que desempenha papel de controle no ciclo celular e no mecanismo de carcinogênese. Este trabalho teve como proposição verificar a correlação clinicopatológica da expressão da survivina nas diferentes condições relacionadas à carcinogênese intra-bucal humana, o que pode ser útil para destacar aspectos importantes das etapas da carcinogênese bucal. Foram constituídos três grupos, formados em parte por material citológico coletado de pacientes participantes do Programa Ambulatorial de Tratamento de Tabagismo do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (INCOR-HCFMUSP); e por material que se encontra incluído em blocos de parafina no Laboratório de Patologia Bucal da Faculdade de Odontologia de São José dos Campos FOSJC - UNESP. O primeiro grupo foi constituído por material citológico obtido do bordo lateral lingual esquerdo e soalho bucal de 30 pacientes que fumavam mais de 20 cigarros/dia/10anos e que não apresentavam histórico de neoplasia bucal maligna, nem sinais clínicos visíveis no local avaliado; o segundo grupo foi constituído por amostras teciduais de 21 pacientes com lesões brancas clinicamente classificadas como leucoplasias. O terceiro grupo foi formado por 42 amostras teciduais de pacientes com diagnóstico de carcinoma epidermóide bucal. Os pacientes que foram submetidos à citologia esfoliativa foram examinados através de anamnese, exame clínico extra e intra -bucal. A citologia esfoliativa foi realizada com cytobrush para obtenção de duas lâminas de cada local selecionado. Após a realização da imunoistoquímica com anticorpo primário anti-survivina as lâminas foram analisadas qualitativamente através da microscopia óptica. Uma lâmina de assoalho e uma de língua foram coradas e avaliadas pelo método de Papanicolaou... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Survivin is an inhibitor of apoptosis protein that plays a role in cell cycle control and the mechanism of carcinogenesis. The aim of the present work was to study the clinicopathological correlation of survivin expression in different conditions related to intra-oral carcinogenesis. This may be useful to highlight important aspects of oral carcinogenesis steps. Three groups were analyzed. They were formed in part by cytological material collected from patients of Heart Institute's Patient Center and the Smoking Cessation Program of the University Hospital, University of São Paulo Medical School (INCOR-HCFMUSP) and material of Laboratory of Oral Pathology, São José dos Campos Dental School. The first group consisted of cytologic material obtained from the left side of the tongue and mouth floor of 30 patients who smoked more than 20 cigarrettes/day/10years and had no history of malignant oral neoplasm or clinical signs at the site evaluated; the second group consisted of tissue samples from 21 patients with white lesions clinically classified as leukoplakia. The third group consisted of 42 tissue samples from patients diagnosed with oral squamous cell carcinoma. Patients who underwent exfoliative cytology were examined by medical history, extra and intra-oral clinical examination. The exfoliative cytology was performed using cytobrush to obtain two smears of each selected location. After performing the immunohistochemistry for anti-survivin the slides were analyzed qualitatively by light microscopy. One smear of mouth floor and tongue was stained and evaluated by the method of Papanicolaou. Statistical analysis was performed by Fisher's exact test, Mann-Whitney and X2. Survivin was positive in 100% of cytological material from the smokers, 85.7% of oral leukoplakia and 83.3% of oral squamous cell carcinoma. Fisher's exact test showed no association between the expression... (Complete abstract click electronic access below) / Orientador: Janete Dias Almeida / Coorientador: Jaqueline Scholz Issa / Banca: Luiz Antonio Guimarães Cabral / Banca: Adriana Aigotti Haberbeck Brandão / Banca: Renata Falchete do Prado / Banca: Suzana Cantanhede Orsini Machado de Sousa / Doutor

Orientador: Luis Fernando Barbisan / Resumo: A capsaicina (8-Metil-N-vanilil-(trans)-6-nonamida) é um composto alcaloide lipofílico e o principal componente responsável pela pungência em pimentas vermelhas, consumidas mundialmente. Estudos sobre o potencial mutagênico e genotóxico da capsaicina apontam resultados inconsistentes e conflitantes. Neste estudo, avaliamos o potencial genotóxico e os mecanismos moleculares envolvidos nos efeitos anti-proliferativos e pró-apoptóticos da capsaicina na carcinogênese de cólon induzida pela 1,2-dimetilhidrazina (DMH) em ratos. Ratos Wistar machos foram randomicamente alocados em seis grupos (n=16). Durante as quatro primeiras semanas do experimento, os grupos 1 e 6 receberam doses intragástricas de óleo de milho (veículo da capsaicina), enquanto a capsaicina foi administrada nas doses de 5mg/kg aos grupos 2 e 4 e 50 mg/kg aos grupos 3 e 5, três vezes por semana. Durante a terceira e quarta semana, todos os animais receberam quatro injeções subcutâneas de DMH (grupos 1-3, 40mg/kg) ou EDTA (grupos 4-6, veículo do DMH), duas vezes por semana. Os animais foram sacrificados 24 horas (n=6) e 22 semanas (n=10) após o tratamento com DMH. Vinte e quatro horas após o tratamento com a DMH, a administração de capsaicina diminuiu significativamente a genotoxicidade induzida pela DMH em leucócitos do sangue periférico, bem como a genotoxicidade da água fecal em células CaCO-2. A capsaicina também reduziu o índice de proliferação de Ki-67 e aumentou a expressão de caspase-3 ativada no cólon dos ... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Made available in DSpace on 2014-06-11T19:27:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-29Bitstream added on 2014-06-13T18:56:50Z : No. of bitstreams: 1 silva_frm_me_botfm.pdf: 2481576 bytes, checksum: 0cc379f4b864c599808f845e21be54a1 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente estudo foi delineado para investigar a possível ação quimioprotetora do quelato de zinco (ZnGly), na etapa de iniciação da carcinogênese do cólon, induzida pela 1,2- dimetilhidrazina (DMH) em ratos Wistar machos. Os animais foram distribuídos em quatro grupos experimentais e receberam três doses de 40mg/Kg, via subcutânea (sc) de DMH ou EDTA (veiculo da DMH) e 15mg/Kg de quelato de zinco (ZnGly) por gavagem durante quatro semanas. Após a narcose foram coletadas amostras de sangue e, em seguida fragmentos do cólon para dosagens de zinco. O cólon foi removido inteiro, fixado em formalina tamponada a 10%, corado com azul de metileno para análise de incidência de focos de criptas aberrantes (FCAs) e processado histologicamente para análise dos índices de proliferação celular e apoptose. A exposição à DMH aumentou significativamente os índices de proliferação celular e apoptose na mucosa do cólon. A administração do quelato de zinco (ZnGly) não alterou o número e multiplicidade de FCAs e não modificou as taxas de proliferação celular e de apoptose da mucosa do cólon, tanto no grupo tratado com DMH como no respectivo grupo controle. Os resultados deste estudo indicam o zinco não mostrou ação protetora na etapa de iniciação da carcinogênese do cólon induzida pela DMH em ratos Wistar machos / The present study was designed to investigate the possible chemopreventive action of zinc gluconate (ZnGly) on the initiation step of colon carcinogenesis induced by 1,2- dimethylhydrazine (DMH) in male Wistar rats. The animals were divided into four groups and received three doses of DMH (40 mg/Kg, s.c) or EDTA (DMH vehicle) and 15 mg/Kg of zinc glycine (ZnGly) administered by gavage for four weeks. After the narcosis, blood and colon fragments samples were collected for zinc dosage. The entire colon was removed, fixed in buffered formalin 10%, stained with methylene blue for the analysis of ACF formation. The rates of cell proliferation and apoptosis were also analyzed in epithelial crypt cells. The exposure to DMH significantly increased the rates of cell proliferation and apoptosis in epithelial cript cells. Treatment with zinc glycine (ZnGly) did not alter the number and multiplicity of ACFs, as well as apoptosis and cell proliferation indices in both DMH-treated and control group. The present findings indicate that zinc did not present chemopreventive effects on the initiation step of DMH-induced colon carcinogenesis in male Wistar rats

Made available in DSpace on 2014-06-11T19:27:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-17Bitstream added on 2014-06-13T19:15:40Z : No. of bitstreams: 1 bidinotto_lt_me_botfm.pdf: 438545 bytes, checksum: 16013851a4d54716162eb93906126f59 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Lemongrass (Cymbopogon citratus STAPF) has been described as a potential chemopreventive agent. Thus, the present study objectives were evaluate the protective effects of oral treatment with lemongrass essential oil (LGEO) on carcinogenesis initiation phase with N-methyl-N-nitrosurea (MNU) and post-initiation carcinogenesis phase in multipleorgans model, through 7,12-dimethylbenz(a)antracene (DMBA), 1,2-dimethylhidrazine (DMH), and N-buthyl-N-(4-hidroxibuthyl)nitrosamine (BBN) administrations in Balb/C female mice. The animals were distributed into 2 experimental protocols. Experiment 1: the animals were allocated into 3 experimental groups: G1A group (negative control), G2A group (treated with LGEO 500 mg/kg b.wt., i.g., during 5 weeks and, at the end of the 3rd and 5th weeks, received one 30 mg/kg MNU i.p. application) and G3A group (treated with the LGEO vehicle, and MNU at the end of the 3rd and 5th weeks). After 4 hours of each MNU application, blood samples were collected to perform the comet assay, and, at the end of the 5th week, all animals were euthanatized and the urinary bladder, mammary glands and colon were collected for histological analysis, apoptosis and cellular proliferation counting. Experiment 2: the animals were allocated into 3 experimental groups: G1B group (positive control, DDB-treated animals), initiated with DMBA (5x1 mg i.g. applications), DMH (4x30 mg/kg s.c. applications) and BBN (8x7.5 mg/kg i.g. applications) and treated with the LGEO vehicle, and G2B and G3B groups, similarly DDB-treated, and treated with 125 mg/kg or 500 mg/kg LGEO respectively (5x/week during 6 weeks). At the end of the experimental period, all animals were euthanatized and urinary bladder, mammary glands and colon were collected for preneoplastic and neoplastic lesions analysis. The LGEO treatment reduced DNA damage in peripheral blood leukocytes as well as mammary gland cellular proliferation index.

Made available in DSpace on 2014-06-11T19:23:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-07-21Bitstream added on 2014-06-13T19:49:40Z : No. of bitstreams: 1 mainenti_p_me_sjc.pdf: 623200 bytes, checksum: d227d4d10a271c7131a651e433d811a0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A carcinogênese consiste em um processo de alterações genéticas após contato celular com agentes físicos, químicos ou biológicos. Esta interação pode culminar em manifestações de fenótipos malignos celulares. No estudo experimental da carcinogênese em glândulas salivares animais, os autores são unânimes em apontar os hidrocarbonetos policíclicos aromáticos (HPA) como potentes agentes carcinogênicos. O 7,12 - dimetilbenzantraceno (DMBA), pertencente ao grupo dos HPA, é considerado o carcinógeno químico de eleição para a tumorigênese de glândulas salivares animais. Este trabalho visou o estudo de DMBA injetado em glândulas salivares submandibulares de ratos. Foram utilizados 28 ratos (Rattus norvegicus), com três meses de idade e peso aproximado de 300g. Os resultados revelaram, na 5ª semana, sete casos de sialadenite crônica. Na 10ª semana, um caso com atipia celular ductal, dois casos de carcinoma epidermóide e quatro de sialadenite crônica. Entre a 15ª e 20ª semanas, foram observados três casos de hiperemia, três casos de carcinoma epidermóide, um caso de sarcoma e sete casos de carcinossarcoma. A análise dos dados, em porcentagem, revelou: 3,6% de atipia celular, 3,6% de sarcoma, 10,7% de hiperemia, 17,9% de carcinoma epidermóide, 25% de carcinossarcoma e 39,4% de sialadenite crônica. Conclusão: Os dados obtidos permitiram o estudo da história natural da carcinogênese glandular por DMBA desde os processos inflamatórios iniciais até à formação de neoplasias mesenquimais, epiteliais e mistas. / The carcinogenesis consists in a process in which the direct contact between cells and some physical, chemical or biological agents results in cell malignization. In the scope of experimental salivary gland carcinogenesis there is a consensus in the use of polycyclic aromatic hydrocarbons (PAH) as carcinogens. The 7,12 - dimethylbenzanthracene (DMBA) is the most used PAH. This paper aims the investigations of the DMBA injected in rats submandibular glands. For this purpose, 28 rats (Rattus norvegicus), three months old (300 gr. weight, approximately) were used. The animals were divided into four groups of seven each. All animals were anesthetized and shaved in the neck. After antisepsis, one ventral neck incision, followed by dissection was performed in each animal. The left submandibular gland was injected with 0.1 ml of 2% DMBA in acetone. The skin was closed with 3-Ø silk suture. By the end of the 5th, 10th, 15th and 20th weeks the animals were sacrificed by lethal doses of anesthetics. The results in the 5th week presented seven cases of chronic sialadenitis. After 10 weeks one case of ductal cell atypia was evident, two cases of squamous cell carcinoma and four cases of chronic sialadenitis were also seen. Between the 15th and 20th weeks the cases were diagnosed as follows: three cases of hyperemia, three cases of squamous cell carcinoma, one case of sarcoma and seven cases of carcinosarcoma. The data analysis showed 3.6% of cellular atypia, 3.6% of sarcoma, 10.7% of hyperemia, 17.9% of squamous cell carcinoma, 25% of carcinosarcoma and 39.4% of chronic sialadenitis. Conclusion: the results allowed the investigation of the glandular carcinogenesis natural history after DMBA injection, from the beginning of inflammatory changes to the neoplastic manifestation of mesenquimal, epithelial and mixed tumours.