Chemical carcinogens

This chapter is part of the book “Oxford Textbook of Oncology” that gives a whole view of cancer, approaching basic concepts of oncology, etiology, epidemiology, care and characteristics of cancer in specific places. It is focused on chemical carcinogens, reviewing the origin of these compounds, their classification and mode of action, their absorption and metabolism, and the methods available to test carcinogenicity. This title includes an extensive list of main chemical compounds and a schematic representation of the absorption and metabolism of direct and indirect chemical carcinogenesis, and the process of carcinogenesis. The title was written for qualified specialist doctors in the oncology research

Anatomia e Fisiologia: evoluindo de “mãos dadas”

A Anatomia e a Fisiologia encontram-se intimamente ligadas e são unidades curriculares fundamentais em inúmeros cursos ligados às ciências da vida. Documentos ancestrais comprovam que a história da Anatomia e da Fisiologia teve início na Grécia e encontra-se associada a Hipócrates (460-370 a.C.), conhecido como o Pai da Medicina, e à sua obra “Corpus Hippocraticus”. O médico grego Claudius Galeno (129-200 d.C.) desenvolveu trabalhos nas áreas da Anatomia e da Fisiologia. Dos resultados das suas experiências em animais surge o conceito de fisiologia experimental. Galeno é considerado o “pai” da fisiologia experimental e a sua obra “Sobre o uso das partes do corpo humano” regeu a Medicina por catorze séculos, após os quais algumas das suas teorias foram contestadas. Os artistas renascentistas, como Leonardo da Vinci e Michelangelo, estudavam os corpos para obter perfeição nas formas artísticas, contribuindo para o desenvolvimento da Anatomia. Em plena época do Renascimento, surgiu pela primeira vez o significado da palavra Fisiologia de acordo com a definição de Jean Fernel (1497-1558). Este ficou conhecido pela célebre frase: “A Anatomia está para a Fisiologia como a Geografia está para a História: ambas descrevem o teatro de operações”. Jean Fernel é o marco entre a medicina medieval e a medicina da idade moderna. Vesalius (1514-1564) corrigiu erros de outros anatomistas e escreveu a obra “De humani corporis fabrica” que contribuiu para o reconhecimento da Anatomia como ciência básica. Já no século XVII, uma das maiores contribuições para a Fisiologia data de 1628, ano da publicação da obra “Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus”, de William Harvey (1578-1657), onde pela primeira vez se descreveu a anatomia e o movimento do coração e a consequente circulação do sangue pelo corpo. O “De Motu Cordis” foi o primeiro tratado da época moderna dedicado a um tema estritamente fisiológico. Em 1876 foi fundada, em Londres, a Sociedade de Fisiologia e em 1887 nos Estados Unidos da América foi fundada a Sociedade de Fisiologia Americana. Ambas se dedicavam à investigação científica, educação e disseminação de conceitos relacionados com a fisiologia. O primeiro Congresso internacional de Anatomia decorreu em 1895, em Basileia

Histopathological features of organs in a rat model of mamamry carcinogenesis: a reference database

Mammary tumors’ development was induced through the intraperioneal administration of the carcinogen N-methyl-N-nitrosourea (MNU). Animals from group control were injected with the vehicle (saline solution). Animals were sacrificed at 25 weeks-old and the organs were histopathologically evaluated. A higher number of lesions was observed in the organs of animals from group MNU. The animals from group control did not present any lesion in lymph nodes. Independently of the experimental group, the internal organs presented hemodynamic alterations, degenerative and inflammatory changes. Hemodynamic changes may be consequence of euthanasia method. As expected, the higher number and the higher grade of the lesions in group MNU were due to the carcinogen administration.info:eu-repo/semantics/publishedVersio

Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs

This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n =11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related.info:eu-repo/semantics/publishedVersio

Realistic aspects behind the application of the rat model of chemically-induced mammary cancer: Practical guidelines to obtain the best results

Cancer is one of the most important public health problems worldwide. Despite the great contribution of in-vitro studies for biomedical research, animals are essential to study diseases’ biopathology and diagnosis, and searching for new preventive and therapeutic strategies. Breast cancer is currently the most common cancer globally, accounting for 12.5% of all new annual cancer cases worldwide. Although the rat model of mammary cancer chemically-induced is widely used to study this disease, there is a lack of standardization in procedures for cancer induction, sample collection, and analysis. Therefore, it is important to provide a practical guide for researchers aiming to work with this model to make the analysis of results more uniform. Thus, in this review, we provide the researchers with a detailed step-by-step guide to implement a rat model of mammary cancer, based on our wide experience in this field, to obtain the best results, maximum throughput of each experiment, and easy comparison among researches

Modelos de cancro da mama: do in vitro para o in vivo

A incidência e mortalidade de cancro da mama têm vindo a aumentar ao longo dos anos. Esta doença foi descrita pela primeira vez no ano 3000 a.C. por Edwin Smith Papyrus como uma doença grave sem tratamento conhecido. Atualmente, continua a ser necessário o delineamento de estratégias de prevenção, deteção e tratamento do cancro da mama. Para tal, é extremamente importante a utilização de modelos alternativos ao Homem. A utilização de animais para fins experimentais iniciou-se há muitos séculos (2000 anos a.C.), com os Babilónios e os Assírios a utilizarem animais para a realização de cirurgias. Os modelos in vitro são relativamente recentes em comparação com os modelos in vivo, uma vez que a primeira linha celular de cancro da mama (BT-20) foi descoberta apenas em 1958 por Lasfargues e Ozzello. Os modelos in vivo são os mais utilizados pois mimetizam quase na sua totalidade o comportamento da neoplasia no organismo. Em 1965, Howell realizou o primeiro estudo de carcinogénese mamária quimicamente induzida em ratos. Posteriormente, surgiu a necessidade da criação de animais geneticamente modificados para reduzir ao máximo as diferenças nos mecanismos tumorais. Mesmo assim, não é possível mimetizar a 100% o processo de carcinogénese humano nestes animais devido à sua elevada complexidade e número limitado de genes. Atualmente existe uma diversidade de modelos in vitro e in vivo para o estudo do cancro da mama. A escolha do modelo animal mais adequado é um dos passos mais importantes no delineamento experimental. Os objetivos do trabalho e o tipo de dados que poderão ser obtidos do modelo animal são aspetos fundamentais a ter em consideração. Todos os modelos apresentam vantagens e desvantagens e a sua seleção merece uma reflexão cuidada à luz dos objetivos do trabalho

Validation of the rat model of prostate cancer: correlating seminal vesicle lesions with dorsolateral prostate lesions

Background/aim: Lesions in the seminal vesicle are described in the most used protocols for prostate cancer (PCa) induction. This study aimed to characterize the lesions of seminal vesicles associated with a protocol of PCa induction in rats to contribute to better characterization of this model. Materials and methods: Forty-five male Wistar Unilever rats were randomly divided into two control groups: CONT1 (n=10) and CONT2 (n=10); and two PCa-induced groups: IND1 (n=10) and IND2 (n=15), sacrificed at 35 and 61 weeks, respectively. Animals from the induced groups were exposed to a multistep protocol for PCa induction. Animals, seminal vesicles and dorsolateral prostate were weighed. Seminal vesicles and dorsolateral prostate were submitted to histopathological and immunohistochemical analysis. Results: Animals in which PCa was induced had a lower mean body weight when compared with the control animals (p<0.05). The relative mean seminal vesicle weight was higher in groups with PCa when compared with control groups (p<0.05). Although the differences were not statistically significant, animals from the IND2 group developed more lesions than animals from the IND1 and CONT2 groups. It is worth noting that the animals from group IND2 developed papillary adenomas and carcinomas in situ, which were not observed in any other group. Similar to observations in seminal vesicles, animals from group IND2 developed more dorsolateral prostate lesions than animals from the IND1 group (p<0.05). Conclusion: We observed that the longer the exposure to testosterone was, the greater was the incidence of preneoplastic and neoplastic lesions in both the seminal vesicle and the prostate, suggesting that testosterone exposure affects the spectrum of developed lesions

Cytokeratin 7/19 expression inN-diethylnitrosamine-induced mouse hepatocellular lesions: implications for histogenesis International

Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome, whose histogenesis is the subject of intense debate. Specifically, expression ofcytokeratins (CKs) 7 and 19, associated with aggressive biological behaviour, is proposed to reflect a possible progenitor cell origin or tumour dedifferentiation towardsa primitive phenotype. This work addresses that problem by studying CKs 7 and 19expression in N-diethylnitrosamine (DEN)-induced mouse HCCs. ICR mice weredivided into six DEN-exposed and six matched control groups. Samples were takenfrom each group at consecutive time points. Hyperplastic foci (13 lesions) occurredat 29-40 weeks (groups 8, 10 and 12) with diffuse dysplastic areas (19 lesions) andwith one hepatocellular adenoma (HCA) (at 29 weeks). HCCs (4 lesions) wereobserved 40 weeks after the first DEN administration (group 12). CKs 7 and 19showed identical expression patterns and located to large, mature hepatocytes, isolated or in small clusters. Hyperplastic foci and the single HCA were consistentlynegative for both markers, while dysplastic areas and HCCs were positive. Theseresults support the hypothesis that CKs 7 and 19 expression in hepatocellular malignancies results from a dedifferentiation process rather than from a possible progenitor cell origin

Anatomy and imaging of rat prostate: practical monitoring in experimental cancer-induced protocols

The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).publishe

Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs

This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n = 11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose relate