2.4.3 3, 4, 9, 10 Dibenzopyrene induced fibrosarcoma in mice:
The C57BL/6 mice develop tumours after receiving a single subcutaneous injection of 500g of 3, 4, 9, 10 Dibenzopyrene in peanut oil. Within 4 to 5 weeks of treatment, all injected animals develop consistent subcutaneous fibro-sarcomas at the injection site. Tumor weight, histological examination of the tumour, including mitotic index, and other evaluation criteria are included. The model has the benefit of being able to produce tumours with a single dosage of carcinogen. Furthermore, carcinogens do not pass through the intestines or urine and remain in the created tumours, making the animals safer to handle(Nicol et al., 2004).
2.5 Transplantable tumors: These models involve cancer cell lines or tissues that can be produced in mice or rats. Transplantation can be done in two ways.
A. Heterotopic transplantation
B. Orthotopic transplantation
A. Heterotopic transplantation: It includes the transplanting of tumour cells or tissue to a location different than the one where they originated. This procedure usually includes i.p. or s.c. transplantation, depending on whether the tumour proliferates as ascites or a solid tumour. This inoculation method is straightforward and quick. As a result, it is now possible to vaccinate a huge number of animals at once. It also demands a restricted skill set and knowledge.
B . Orthotopic transplantation: It is the process of transplanting tumor cells to the anatomic region or tissue from where a tumour originated. A lung tumour, for example, is transplanted into the lungs. In terms of histology, vascularity, gene expression, chemotherapeutic responsiveness, and spreading behaviour, this technique has produced tumour models that are more similar to human tumours. Orthotopic malignancies are preferable over standard flank (s.c. transplant) models as more is learned about host-microenvironment interaction. The cancer cells can be transplanted orthotopically by (ii) direct injection of tumour cells or (ii) surgical orthotopic implantation (SOI), which is the surgical implantation of entire tumour pieces orthotopically(Khanna and Hunter, 2005).The use of SOI increases the model’s repeatability and metastatic result. Furthermore, transplantable models can be divided into two groups based on the source of the tumour and the host used.
2.5.1 Syngenic models: In these models, cancer cell lines or tissues from mice or rats (murine) are transplanted into inbreed animals that share the cell line’s or tissue’s genetic background. For instance, the DBA/2 mouse was used to create the L1210 leukemic cell line, which was then expanded under the same circumstances. These are cancer cell lines that have either grown on their own or as a result of exposure to toxins. Mice with the same genetic makeup as the tumours can be given injections of these cell lines or fresh tumour samples. The host, transplanted tissues, and tumour microenvironment are all members of the same species in syngeneic models. Given the close connection between the tumour and the host, this is especially important. On the other hand, these model systems don’t have many of the essential characteristics of actual tumours. They lack the genetic complexity of human tumours because they are frequently created from homozygously inbred mice. Additionally, they might not have the same constellation of mutations as patients with human mutations due to differences in oncogenesis between species(Voskoglou-Nomikos et al., 2003).
2.5.1.1 Leukemia 1210 (L1210): The DBA/2 mouse served as the implantation host. Following the injection of 0.2 percent 20-methylcholanthrene to the epidermis of a female DBA/2 mouse, the tumour developed, which was then transplanted subcutaneously/intramuscularly and obtained in ascitic form(DeVita and Chu, 2008).
The both subcutaneous transplantation of solid tumour fragments into the flank region and intraperitoneal injection of leukemic cells are transplantation techniques. The peritoneum undergoes a period of rapid development after i.p. inoculation. After spreading both in solid and ascitic forms, animals are killed between 9 and 12 days later. The mean survival time (MST) of the ascitic form is influenced by the size of the inoculum. This strategy is very helpful when pre-screening test substances. This model allows for the processing of many different compounds at a low cost. But it was later found that selecting for drugs that are preferentially active against quickly expanding malignancies was skewed by screening for rapidly increasing leukemic cells. If effective treatments for solid tumours could be developed, a different approach would almost certainly be required(DeVita and Chu, 2008).
2.5.1.2 Lewis Lung Carcinoma model: In 1951, Dr. Margaret R. Lewis discovered a spontaneous epidermoid lung cancer in a C57BL/6 mouse. Common transplant procedures include the subcutaneous transplantation of tumour tissue fragments and the anesthesia-induced injection of tumour cells in suspension into the right main stem bronchus of the lungs. Lower rates of metastatic disease have been achieved by both of these tactics(Rashidi et al., 2000). By surgically orthotopically transplanting tumour fragments or injecting a tumour cell suspension into the tail vein, the tumor’s metastatic potential is significantly reduced. For research on metastasis and angiogenesis, it has served as a tumour model. To make distant metastases visible, the fluorescent protein-coding FP gene is inserted into the cells. This is accomplished by using a retroviral vector, which transects lung cancer cells(O’Reilly et al., 1994).