Experimental model of pulmonary carcinogenesis in Wistar rats

Abstract

Purpose:To elaborate an experimental model of pulmonary carcinogenesis in Wistar rats. Methods: Male Rattus norvegicus albinus, Wistar lineage was carried through an intra-pulmonary instillation of the Benzo[a]pyrene (B[a]P) dilution in alcohol 70%, a polycyclic aromatic hydrocarbon widely known by its power of tumoral induction. Three experimental groups had been formed with 08 animals each: Control Group (Alcohol 70%); B[a]P Group 10 mg/kg; e B[a]P Group 20mg/ kg, submitted to euthanasia 08, 10, 12 and 14 weeks after the experimental procedure. The pulmonary sections had been colored by hematoxilin-eosin (HE) and submitted to the morphometrical analysis to describe the tissue alterations. Results: The presence of diffuse inflammatory alterations was observed in all groups, however, at the analysis of the pulmonary tissue of the experimental groups, it had been observed hyperplasic alterations (BALT hyperplasia), and in one of the animals of the experimental group 20mg/kg (12 weeks), it was noticed the presence of cellular epithelial tracheal pleomorphism, suggesting the adenocarcinoma formation in situ. Conclusion: The main secondary alterations to the intra-pulmonary instillation of B[a]P in Wistar rats were: cellular proliferation, inflammatory alterations of several degrees and nodular lymphoid hyperplasias. The association of an activator agent of the pulmonary metabolic reply is necessary to establish the ideal reply-dose to the development of the lung cancer. Key words: Carcinogenesis. Lung Cancer. Benzo[a]pyrene. Neoplasms. Experimental model. RESUMOObjetivo: Elaborar um modelo experimental de carcinogênese pulmonar em ratos wistar. Métodos: Rattus norvegicus albinus, linhagem Wistar foram submetidos a instilação intra-pulmonar da diluição em álcool 70% de Benzo[a]pireno (B[a]P), um hidrocarboneto aromático policíclico amplamente conhecido por seu poder de indução tumoral. Foram formados três grupos experimentais com 08 animais cada: Grupo Controle (álcool 70%); Grupo B[a]P 10 mg/kg; e Grupo B[a]P 20mg/ kg, submetidos a eutanásia 08, 10, 12 e 14 semanas após o procedimento experimental. As secções pulmonares foram coradas por HE e submetidas a análise morfométrica para descrição das alterações teciduais. Resultados: em todos os grupos observou-se a presença de alterações inflamatórias difusas, porém na análise do tecido pulmonar dos grupos experimentais, observou-se alterações hiperplásicas (hiperplasia de BALT), e em um dos animais do grupo experimental 20mg/kg (12 semanas) notou-se a presença de pleomorfismo celular epitelial traqueal, sugerindo a formação de adenocarcinoma in situ. Conclusão: as principais alterações secundárias à instilação intra-pulmonar de B[a]P em ratos Wistar foram: proliferação celular, alterações inflamatórias de diversos graus e hiperplasias nodulares linfóides. A associação de um agente ativador da resposta metabólica pulmonar pode ser necessária para estabelecimento da dose-resposta ideal ao desenvolvimento do câncer de pulmão. Descritores: Carcinogênese. Câncer de...

Bronchus-Associated Lymphoid Tissue (BALT)

“…As mentioned in previous sections, the formation of BALT is often associated with pulmonary inflammation and exposure to a wide variety of inflammatory stimuli. Thus, it is not particularly surprising that the pulmonary administration of Benzo[a]pyrene (B[a]P) leads to the development of BALT hyperplasia in Wistar rats (Silva et al, 2007). However, B[a]P is also associated with tumorigenesis and can induce pulmonary adenocarcinoma (Silva et al, 2007).…”

“…Thus, it is not particularly surprising that the pulmonary administration of Benzo[a]pyrene (B[a]P) leads to the development of BALT hyperplasia in Wistar rats (Silva et al, 2007). However, B[a]P is also associated with tumorigenesis and can induce pulmonary adenocarcinoma (Silva et al, 2007). Thus, inflammatory responses in the lung can simultaneously promote BALT and neoplasia.…”

Lung apoptosis after intra-pulmonary instillation of Benzo(a)pyrene in Wistar rats

“…Focal inflammatory areas were frequently observed in previous studies involved experimental models of lung cancer. In this study, apoptotic cells presence in all groups may be explained by inflammatory process secondary to cancer induction method 5 . Repair after an acute lung injury requires the elimination of inflammatory cells from the alveolar airspace or alveolar wall.…”

“…Environmental air pollution and smoking habits are the main sources of inhalation exposure to carcinogenic agents such as polycyclic aromatic hydrocarbons (PAH), products of incomplete combustion of organic matter and are widespread in the environment. PAHs, such benzo[a]pyrene (B[a]P), are currently recognized as one of major classes of environmental carcinogenic pollutants 5 .…”

Desenvolvimento de material educativo digital para divulgação científica da nutrigenômica

“…(RIBARREN et al, 1999;KAZEROUNI et al, 2001;GUO et al, 2009). Os HAP podem provocar danos no DNA, favorecendo o desencadeamento de diversos tipos de câncer como, por exemplo, o de pulmão, mama e inclusive de fígado (SILVA et al, 2007;GUO et al, 2009 BRANDÃO, 2003;O´DAY, 2006). Além disso, a disponibilização das animações livremente na internet permite maior acesso ao material educativo digital.…”