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).